EP1730147B1 - Substituted 1,4,8-triazaspiro[4,5]decan-2-on compounds for use in the treatment of obesity - Google Patents

Substituted 1,4,8-triazaspiro[4,5]decan-2-on compounds for use in the treatment of obesity Download PDF

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EP1730147B1
EP1730147B1 EP05716285A EP05716285A EP1730147B1 EP 1730147 B1 EP1730147 B1 EP 1730147B1 EP 05716285 A EP05716285 A EP 05716285A EP 05716285 A EP05716285 A EP 05716285A EP 1730147 B1 EP1730147 B1 EP 1730147B1
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Prior art keywords
triazaspiro
decan
residue
phenyl
benzyl
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French (fr)
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EP1730147A1 (en
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Corinna Sundermann
Bernd Sundermann
Stefan OBERBÖRSCH
Werner Englberger
Hagen-Heinrich Hennies
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Gruenenthal GmbH
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Gruenenthal GmbH
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
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    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid

Definitions

  • the present invention relates to substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds, processes for their preparation, medicaments containing this compound and the use of these compounds for the preparation of medicaments.
  • An object of the present invention was therefore to provide compounds which are particularly suitable as pharmaceutical active ingredients in medicaments, preferably in medicaments for the prophylaxis and / or treatment of obesity.
  • substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of general formula I given below are not only for the regulation, preferably for the inhibition, of serotonin (5-hydroxytryptophan) - Recovery and / or regulation, preferably for inhibition, the norepinephrine reuptake are suitable, but also have a high affinity for opioid receptors, in particular for ⁇ -opioid receptors and for batrachotoxin (BTX) receptors and therefore in particular as pharmaceutical active ingredients in medicaments for prophylaxis and / or treatment of disorders associated with these receptors or processes
  • radicals R 1 to R 9 are alkyl, alkenyl or alkynyl radical or has such a radical
  • Alkenyl radicals have at least one C-C double bond and alkynyl radicals have at least one C-C triple bond.
  • Suitable alkyl, alkenyl and alkynyl radicals which may be monosubstituted or polysubstituted may be selected, for example, from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl Butyl, n-pentyl, iso-pentyl, neo-pentyl, sec-pentyl, 2,2-dimethyl-propyl, 1-methyl-butyl, 1-ethyl-propyl, 1-propyl-butyl, 1-ethyl-pentyl, Penta-1,3-dienyl, n-hexyl, 2-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, - (CH 2 ) - (CH) (C 2 H
  • the alkyl, alkenyl and alkynyl radicals present in accordance with the invention may also contain one or more heteroatoms, preferably one or more oxygen atoms and / or one or more sulfur atoms, more preferably 1 or 2 oxygen atoms and / or 1 or 2 sulfur atoms, as chain link (s).
  • these heteroatoms are in a non-terminal position of the respective moiety.
  • radicals such as -CH 2 -CH 2 -S-CH 3 , -CH 2 -O-CH 2 -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 may be mentioned .
  • R 3 or R 4 is a cycloaliphatic radical or has a cycloaliphatic radical
  • cycloaliphatic radicals are understood as meaning both saturated and unsaturated radicals.
  • the cycloaliphatic radicals may optionally have one or more heteroatoms, preferably 1, 2, 3, 4 or 5 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, as ring members.
  • Suitable cycloaliphatic radicals which may be monosubstituted or polysubstituted may be selected, for example, from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl , Morpholinyl, piperazinyl, thiomorpholinyl, tetrahydropyranyl, azepanyl, diazepanyl and dithiolanyl.
  • the cycloaliphatic radicals can further be at least singly bridged by a linear or branched alkylene group, preferably bridged by one or two linear or branched C 1-5 alkylene groups.
  • Examples of such cycloaliphatic radicals are the 4,7,7-trimethyl-3-oxo-2-oxa-bicyclo [2.2.1] heptyl or adamantyl radical mentioned.
  • R 1 -R 4 , R 7 and R 8 is an aryl or heteroaryl radical or has an aryl or heteroaryl radical
  • furanyl and benzyl may be selected from the group consisting of 1, 2, 3, 4 or 5 substituents independently of one another F, Cl, Br, -OH, -CF 3 , -SF 5 , -CN, -NO 2 , -OC 1-5 alkyl, -C 1-5 alkyl, -O-CF 3 , -S-CF 3 , phenyl and -O-benzyl.
  • phenyl and phenoxy substituents may themselves be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -S-CHF 2 , -CF 3 , -CHF 2 , -CH 2 F , -CN, -NO 2 , C 1-5 alkyl and C 1-5 alkoxy.
  • heteroatoms of the heteroaryl radical can preferably be selected from the group consisting of oxygen, nitrogen and sulfur.
  • the heteroaryl radicals may have 1, 2, 3, 4 or 5 heteroatom (s) independently selected from the group consisting of oxygen, nitrogen and sulfur as the ring member (s).
  • Suitable aryl radicals may preferably be selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl.
  • Suitable heteroaryl radicals may preferably be selected from the group consisting of pyrrolyl, indolyl, furyl (furanyl), benzofuranyl, thienyl (thiophenyl), benzothienyl, pyrazolyl, imidazolyl, thiazolyl, thiadiazolyl, triazolyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl , Pyrazinyl, pyranyl, indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl, quinazolinyl, carbazolyl, phenazinyl, phenothiazinyl and oxadiazolyl, benzo [1,3] dioxolyl, benzo [1,2,5] oxadiazolyl and chromanyl and isoindolyl.
  • a monocyclic ring system is understood as meaning a monocyclic hydrocarbon radical which may be saturated, unsaturated or aromatic and may optionally have one or more heteroatoms as ring members.
  • Such a monocyclic ring system may, for example, be condensed with an aryl radical or a heteroaryl radical, ie be fused or bonded.
  • the heteroatoms of such a monocyclic ring system may each preferably be selected from the group consisting of oxygen, nitrogen and sulfur.
  • the ring of the ring system may have 1, 2, 3, 4 or 5 heteroatom (s) independently selected from the group consisting of oxygen, nitrogen and sulfur as the ring member (s).
  • the ring of the ring system is 5- or 6-membered or 7-membered.
  • R 1 -R 4 has a linear or branched alkylene, alkenylene or alkynylene group, this may-unless stated otherwise-be unsubstituted or monosubstituted or polysubstituted, preferably with 1, 2, 3, 4 or 5 substituents, wherein the substituents can be independently selected from the group consisting of F, Cl, Br, C 1-6 alkoxy, hydroxy, CN, CF 3 , CHF 2 , CH 2 F, unsubstitulertem phenyl and NR a R b , wherein each of R a and R b can be independently selected from the group consisting of H, C 1-3 alkyl and unsubstituted phenyl.
  • the alkylene group may also have one or more heteroatoms, preferably at least one oxygen atom and / or at least one sulfur atom, more preferably 1 or 2 oxygen atom (s) and / or sulfur atom (s), as a chain member (s).
  • An alkenylene group has at least one carbon-carbon double bond
  • an alkynylene group has at least one carbon-carbon triple bond.
  • alkylene, alkenylene or alkynylene groups may, unless stated otherwise, also one or more heteroatoms, preferably one or more, for example 1 or 2, oxygen atoms and / or one or more, for example 1 or 2, sulfur atoms, as Chain link (he) have.
  • R 1 is a hydrogen radical, a linear or branched, unsubstituted, optionally at least one heteroatom C 1-10 -alkyl radical which has a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as chain link, C 2-10 -alkenyl radical, a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkynyl radical, an unsubstituted or at least monosubstituted, 5- to 14-membered aryl or heteroaryl radical which is a linear or branched, optionally at least one heteroatom as a chain member having C 1-5 alkylene group is bound for a via a linear or branched C 1-5 alkylene group bound
  • R 3 is a hydrogen radical, a linear or branched, unsubstituted or at least monosubstituted , optionally at least one heteroatom as a chain member C 1-10 alkyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkenyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkynyl radical, an unsubstituted or at least monosubstituted 5- to 14-membered aryl or Heteroaryl radical which is attached via a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a
  • substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I given above in which the radical R 4 for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 1-10 alkyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkenyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkynyl radical, for an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl radical which has a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 1-5 alky
  • substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I given above in which the radicals R 5 and R 6 , in each case independently of one another, represent a linear or branched C 1 5- alkyl radical, a linear or branched C 2-5 alkenyl radical or a linear or branched C 2-5 alkynyl radical, preferably a methyl, ethyl, n-propyl or iso-propyl Rest are, and in each case the remaining radicals R 1 -R 4 and R 7 -R 9 have the abovementioned meaning, in each case optionally in the form of one of their pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers , in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding
  • radical R 9 is a linear or branched C 1-5 -alkyl radical, a linear or branched chain radical branched C 2-5 alkenyl radical, a linear or branched C 2-5 alkynyl radical, preferably represents a methyl, ethyl, n-propyl or iso-propyl radical, and in each case the other radicals R 1 R 8 have the abovementioned meaning, in each case optionally in the form of one of their pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case Form of corresponding salts, or in each case in the form of corresponding solvates.
  • a further subject of the present invention is a process for the preparation of the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds according to the invention, according to which a protected piperidin-4-one of the general formula 11 wherein P is a protective group, by reaction with at least one compound of general formula III, in which R 2 has the abovementioned meaning, in at least one compound of the general formula IV, wherein P and R 2 have the abovementioned meaning, which is optionally purified and / or optionally isolated, and optionally by reaction with at least one compound of general formula R 1 -X 1 , wherein R 1 has the abovementioned meaning and X 1 is a suitable leaving group, preferably a halogen radical, optionally in the presence of at least one base, in at least one compound of general formula V, wherein R 1 , R 2 and P have the abovementioned meaning, is converted, and this optionally purified and / or optionally isolated, and optionally by cleavage of the protective group
  • N-protected piperidin-4-one compounds of general formula II are - as well as unprotected piperidin-2-one and corresponding salts such as its hydrochloride - commercially available on the market or can be prepared by conventional methods known in the art.
  • Suitable protecting groups are, for example, trifluoroacetamide, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, allyloxycarbonyl or 9-fluorenylmethoxycarbonyl,
  • amino acid amides of general formula III which can also be used in the form of their corresponding salt in the process according to the invention, are likewise commercially available or can be prepared by customary methods known to the person skilled in the art.
  • the respective amino acid amides can be used in the inventive method both in enantiomerically pure form, ie in ( S ) - or ( R ) - configuration, or in the form of a preferably racemic mixture with ( S, R ) configuration.
  • reaction of compounds of general formula II with compounds of general formula III to give N-protected, optionally substituted in 3-position, 1,4,8-triaza-spiro [4.5] decan-2-one compounds of general formula IV under customary conditions known to those skilled in the art.
  • the reaction is carried out in a suitable reaction medium, for example in one or more dry organic solvents.
  • suitable solvents are, for example, alcohols such as ethanol or chlorinated hydrocarbons such as methylene chloride or chloroform.
  • the temperature during the annealing and reaction of the reaction components can vary over a wide range.
  • the general formula V is preferably carried out in a reaction medium in the presence of at least one organic base and / or in the presence of at least one inorganic base under conventional conditions known in the art.
  • the reaction can be advantageously carried out in the microwave.
  • Suitable inorganic bases are, for example, metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, lithium or sodium bases such as lithium diisopropylamide, butyllithium, tert-butyllithium, sodium methylate or metal hydrides such as potassium hydride, lithium hydride, sodium hydride.
  • Suitable organic bases include, for example, diisopropylethylamine or triethylamine.
  • Suitable reaction media are organic solvents such as tetrahydrofuran.
  • the cleavage of the protective group (P) for the preparation of N-unprotected, optionally substituted in 1 and / or 3-position 1,4,8-triaza-spiro [4.5] decan-2-one compounds of general formula VI can also be carried out under customary conditions known in the art, which vary depending on the protecting group used.
  • Examples are the cleavage in the presence of an inorganic base, acid or Lewis acid, such as potassium carbonate, lithium hydroxide, potassium hydroxide, sulfuric acid, hydrobromic acid, hydrofluoric acid, hydrochloric acid, boron trifluoride etherate, boron trichloride, an organic acid such as trifluoroacetic acid, trifluoromethanesulfonic acid, acetic acid, the cleavage in the presence of a organic base such as morpholine, triethylamine, diethylamine, diisopropylethylamine, pyridine or hydrogenation.
  • an inorganic base acid or Lewis acid, such as potassium carbonate, lithium hydroxide, potassium hydroxide, sulfuric acid, hydrobromic acid, hydrofluoric acid, hydrochloric acid, boron trifluoride etherate, boron trichloride, an organic acid such as trifluoroacetic acid, trifluoromethanesulfonic acid,
  • a suitable leaving group preferably a halogen radical
  • reaction of compounds of the general formula IV, V or VI, in particular of compounds of the general formula VI, to give a substituted 1,4,8-triaza-spiro [4.5] decan-2-one compound of the general formula I according to the invention is preferably carried out in a suitable reaction medium, for example in one or more dry organic solvents.
  • suitable solvents are, for example, optionally chlorinated, possibly aromatic hydrocarbons such as toluene, methylene chloride or chloroform.
  • the temperature during the annealing and reaction of the reaction components can vary over a wide range.
  • Suitable bases include diisopropylethylamine, triethylamine, pyridine or diethylamine.
  • suitable organic bases are Diisopropylethylamine, triethylamine, pyridine or diethylamine called.
  • Preferred reaction media are dried organic solvents such as, for example, trophic tetrahydrofuran.
  • reaction of compounds of general formula VIII with compounds of general formula III to give substituted in 3-position 1,4,8-triaza-spiro [4.5] decane-2-one compounds of general formula IX can under conventional, known in the art Conditions are fulfilled.
  • the reaction is carried out in a suitable reaction medium, for example in one or more dry organic solvents.
  • suitable solvents are, for example, alcohols such as ethanol or chlorinated hydrocarbons such as methylene chloride or chloroform.
  • the temperature during the annealing and reaction of the reaction components can vary over a wide range.
  • the reaction of a substituted in 3-position 1,4,8-triaza-spiro [4.5] decan-2-one compound of general formula IX with a compound of general formula R 1 -X 1 to a 1,4,8 according to the invention -triaza-spiro [4.5] decan-2-one compound is preferably carried out in a reaction medium in the presence of at least one organic base and / or in the presence of at least one inorganic base under customary conditions known to the person skilled in the art.
  • the reaction can be advantageously carried out in the microwave.
  • Suitable inorganic bases are, for example, metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, lithium or sodium bases such as lithium diisopropylamide, butyllithium, tert-butyllithium, sodium methylate or metal hydrides such as potassium hydride, lithium hydride, sodium hydride.
  • Suitable organic bases include, for example, diisopropylethylamine or triethylamine.
  • Suitable reaction media are organic solvents such as tetrahydrofuran.
  • X 1 and X 2 are customary, known in the art leaving groups, preferably halogen radicals, more preferably chlorine radicals.
  • the intermediate and end products obtained according to the above-described reactions can each be purified and / or isolated, if desired and / or required, by customary methods known to those skilled in the art. Suitable purification methods are, for example, extraction methods and chromatographic methods, such as column chromatography or preparative chromatography.
  • substituted 1,4,8-triaza-spiro [4.5] decan-2-one compounds of general formulas I above and optionally corresponding stereoisomers in each case can be prepared by customary methods known to the person skilled in the art in the form of appropriate salts, in particular in the form of corresponding physiologically acceptable salts are obtained, wherein the medicament of the invention may comprise one or more salts of one or more of these compounds.
  • Suitable acids may preferably be selected from the group consisting of perchloric, hydrochloric, hydrobromic, sulfuric, methanesulfonic, formic, acetic, oxalic, succinic, tartaric, mandelic, fumaric, lactic, citric, glutamic, succinic, cyclohexanesulfamic, aspartame, monomethylsebacic, 5 Oxo-proline, hexane-1-sulfonic acid, nicotinic acid, 2-aminobenzoic acid, 3-aminobenzoic acid or 4-aminobenzoic acid, 2,4,6-trimethylbenzoic acid, ⁇ -lipoic acid, acetylglycine, hippur
  • substituted 1,4,8-triaza-spiro [4.5] decan-2-one compounds of the general formula I above and optionally corresponding stereoisomers and in each case their physiologically acceptable salts can also be prepared by conventional methods known to the person skilled in the art in the form of theirs Solvates, especially in the form of their hydrates can be obtained.
  • substituted 1,4,8-triaza-spiro [4.5] decan-2-one compounds of the general formula I according to the invention after their preparation in the form of a mixture of their stereoisomers, preferably in the form of their racemates or other mixtures of their different enantiomers and / or diastereomers are obtained, these can be separated by conventional methods known in the art and optionally isolated. Examples which may be mentioned are chromatographic separation processes, in particular liquid chromatography processes under atmospheric pressure or under elevated pressure, preferably MPLC and HPLC processes, and also fractional crystallization processes. In particular, single enantiomers, e.g. be separated by chiral HPLC or by crystallization with chiral acids, such as (+) - tartaric acid, (-) - tartaric acid or (+) - 10-camphorsulfonic acid formed diastereomeric salts.
  • the 1,4,8-triazaspiro [4.5] decan-2-one compounds of the above-indicated general formula I are not only useful for regulating, preferably for inhibiting, norepinephrine reuptake and / or for regulating, preferably for inhibition, the 5-hydroxy-tryptophan reuptake are suitable, but also have a high affinity for opioid receptors, in particular for ⁇ -opioid receptors and for batrachotoxin (BTX) receptors and therefore in particular as pharmaceutical agents in medicaments for the prophylaxis and / or treatment of disorders associated with these receptors or processes.
  • BTX batrachotoxin
  • Another object of the present invention is therefore a medicament containing at least one inventive 1,4,8-triazaspiro [4.5] decan-2-one compound of the above general formula I, optionally in the form of one of its pure stereoisomers, especially enantiomers or Diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate, and optionally at least one pharmaceutically compatible excipient.
  • inventive 1,4,8-triazaspiro [4.5] decan-2-one compound of the above general formula I optionally in the form of one of its pure stereoisomers, especially enantiomers or Diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio
  • medicaments which comprise at least one 1,4,8-triazaspiro [4.5] decan-2-one compound of the abovementioned general formula I with the exception of the compounds according to A) and / or with the exception of the compounds according to B), if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in Form of a corresponding solvate, and optionally contain at least one pharmaceutically acceptable excipient.
  • the medicament according to the invention is preferably suitable for the regulation, in particular for the inhibition, of norepinephrine reuptake (norepinephrine uptake), for the regulation, in particular for the inhibition, of 5-hydroxy-tryptophan reuptake (5-HT-uptake), for the opioid receptor -Regulation, in particular for ⁇ -opioid receptor regulation and / or for batrachotoxin (BTX) receptor regulation.
  • norepinephrine reuptake norepinephrine reuptake
  • 5-HT-uptake 5-hydroxy-tryptophan reuptake
  • opioid receptor -Regulation in particular for ⁇ -opioid receptor regulation and / or for batrachotoxin (BTX) receptor regulation.
  • the medicament according to the invention is likewise preferably suitable for the prophylaxis and / or treatment of disorders of food intake, preferably selected from the group consisting of bulimia, anorexia, obesity and cachexia, particularly preferably for the prophylaxis and / or treatment of obesity.
  • the medicament according to the invention is likewise preferably suitable for the prophylaxis and / or treatment of pain, preferably for the treatment and / or prophylaxis of acute pain, chronic pain, neuropathic pain and / or cluster headache, or for the prophylaxis and / or treatment of depression.
  • the medicament according to the invention is particularly preferably suitable for the combined prophylaxis and / or treatment of depression and pain, preferably for the combined treatment of depression and pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and cluster headache.
  • the medicament of the invention is suitable for the prophylaxis and / or treatment of alcohol and / or drug and / or drug abuse, for the prophylaxis and / or treatment of alcohol and / or drug and / or drug dependence, for prophylaxis and / or Treatment of inflammation, for the prophylaxis and / or treatment of listlessness, for the prophylaxis and / or treatment of catalepsy, for vigilance enhancement, for libido enhancement, for anxiolysis, for the prophylaxis and / or treatment of neurodegenerative diseases, preferably one or more neurodegenerative diseases selected from Group consisting of Parkinson's disease, Huntington's disease, Alzheimer's disease and multiple sclerosis, for the prophylaxis and / or treatment of ischaemias and / or local anesthetics.
  • neurodegenerative diseases preferably one or more neurodegenerative diseases selected from Group consisting of Parkinson's disease, Huntington's disease, Alzheimer's disease and multiple sclerosis, for the
  • Another object of the present invention is the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of general formula I according to the invention, optionally in the form of one of its pure stereoisomers, especially enantiomers or diastereomers, of their Racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate, for the preparation of a medicament for the regulation of noradrenaline Recovery (norepinephrine uptake), preferably for the inhibition of norepinephrine reuptake (norepinephrine uptake), for the regulation of 5-hydroxy-tryptophan reuptake (5-HT-uptake), preferably for the inhibition of 5-hydroxy-tryptophan reuptake (5-HT-uptake), for opioid
  • At least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate for the preparation of a medicament for the prophylaxis and / or treatment of depression.
  • At least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form a mixture of stereoisomers, in particular of the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate for the preparation of a medicament for the combined prophylaxis and / or treatment of depression and Pain, preferably for the combined treatment of depression and pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and cluster headache.
  • At least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form a mixture of stereoisomers, in particular of the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate, for the preparation of a medicament for the prophylaxis and / or treatment of alcohol and / or drug and / or drug abuse, for the prophylaxis and / or treatment of alcohol and / or drug and / or drug dependence, for the prophylaxis and / or treatment of inflammation, for the prophylaxis and / or treatment of listlessness, for prophylaxis and / or, for the prophylaxis
  • Particular preference may also be given in each case to the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention with the exception of the compounds according to A) and / or with the exception of the compounds according to B), in each case optionally in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate, for the preparation of a medicament for the prophylaxis and / or treatment of the abovementioned diseases or disorders.
  • the pharmaceutical composition of the invention is suitable for administration to adults and children, including infants and babies.
  • the medicament according to the invention can be used as a liquid, semisolid or solid dosage form, for example in the form of injection solutions, drops, juices, syrups, sprays, suspensions, tablets, patches, capsules, patches, suppositories, ointments, creams, lotions, gels, emulsions, aerosols or in multiparticulate form, for example in the form of pellets or granules, optionally compressed into tablets, filled into capsules or suspended in a liquid, are present and as such also administered.
  • the substituted 1,4,8-triazaspiro [4,5] decan-2-one compounds of the general formula I above if appropriate in the form of their pure stereoisomers, in particular enantiomers or diastereomers, of the abovementioned pharmaceutical compositions Racemates or in the form of mixtures of stereoisomers, in particular the enantiomers or diastereomers, in any mixing ratio, or optionally in the form of a corresponding salt or in each case in the form of a corresponding solvate the medicament of the invention usually further physiologically acceptable pharmaceutical excipients, which may be preferably selected from the group consisting of excipients, fillers, solvents, diluents, surfactants, dyes, preservatives, blasting agents, lubricants, lubricants, flavors and binders.
  • physiologically acceptable excipients depend on whether the drug is oral, subcutaneous, parenteral, intravenous, intraperitoneal, intradermal, intramuscular, intranasal, buccal, rectal or topical, for example, skin infections, mucous membranes and on the eyes, to be applied.
  • Preparations in the form of tablets, dragees, capsules, granules, pellets, drops, juices and syrups are preferred for oral administration, solutions, suspensions, readily reconstitutable dry preparations and sprays for parenteral, topical and inhalative administration.
  • substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds used in the medicament according to the invention in a depot in dissolved form or in a plaster, optionally with the addition of skin penetration-promoting agents, are suitable percutaneous administration preparations .
  • Orally or percutaneously applicable formulations may also release the respective substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds with a delay.
  • compositions of the invention are prepared by conventional means, devices, methods and procedures well known in the art, as described, for example, in "Remington's Pharmaceutical Sciences", published by AR Gennaro, 17th Edition, Mack Publishing Company, Easton, Pa. 1985, in particular in Part 8, Chapters 76 to 93 are described. The corresponding description is hereby incorporated by reference and is considered part of the disclosure.
  • the amount of the respective substituted 1,4,8-triazaspiro [4.5] decan-2-one compound to be administered to the patient may vary and depends, for example, on the weight or age of the patient as well as on the mode of administration, the indication and the severity of the disease Illness. Usually, 0.005 to 50 mg / kg, preferably 0.05 to 50 mg / kg of body weight of the patient of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound according to the invention are administered.
  • mice weighing 25 to 30 g are used.
  • 10 minutes after intravenous administration of the test substances groups of 10 animals per substance dose receive 0.3 ml / mouse of a 0.02% strength aqueous solution of phenylquinone (phenylbenzoquinone, Sigma, Deisenhofen, preparation of the solution with addition of 5% ethanol and storage in a water bath at 45 ° C) intraperitoneally.
  • the animals are placed individually in observation cages.
  • % H ⁇ e ⁇ m ⁇ m ⁇ u ⁇ n ⁇ G 100 - W ⁇ r ⁇ i ⁇ t ⁇ H ⁇ i ⁇ n ⁇ G ⁇ r ⁇ e ⁇ a ⁇ k ⁇ t ⁇ i ⁇ O ⁇ n ⁇ e ⁇ n d ⁇ e ⁇ r b ⁇ e ⁇ H ⁇ a ⁇ n ⁇ d ⁇ e ⁇ l t ⁇ e ⁇ n T ⁇ i ⁇ e ⁇ r ⁇ e * 100 W ⁇ r ⁇ i ⁇ t ⁇ H ⁇ i ⁇ n ⁇ G ⁇ r
  • the ED 50 values with 95% confidence interval of the writhing reaction are calculated from the dose-dependent decrease of the writhing reactions in comparison to parallel examined phenylquinone control groups by regression analysis (evaluation program Martens EDV Service, Eckental).
  • the receptor affinity for the human ⁇ -opioid receptor is determined in a homogeneous batch in microtiter plates.
  • dilution series of the substances to be tested are prepared with a receptor membrane preparation (15-40 ⁇ g protein / 250 ⁇ l incubation mixture) of CHO-K1 cells which express the human ⁇ -opioid receptor (RB-HOM receptor membrane preparation from NEN, Zaventem, Belgium) in the presence of 1 nmol / l of the radioactive ligand [ 3 H] -naloxone (NET 719, NEN, Zaventem, Belgium) and 1 mg of WGA-SPA beads (Wheat germ agglutinin SPA beads from Amersham / Pharmacia, Freiburg, Germany) in a total volume of 250 ⁇ l for 90 minutes at room temperature.
  • Incubation buffer is 50 mmol / l Tris-HCl supplemented with 0.05% (w / v) sodium azide and 0.06% (w / v) bovine serum albumin.
  • an additional 25 ⁇ mol / I naloxone is added.
  • the microtiter plates are centrifuged for 20 minutes at 1000 g and the radioactivity in a ⁇ -counter (Microbeta-Trilux, PerkinEImer Wallac, Freiburg, Germany) measured. The percentage displacement of the radioactive ligand from its binding to the human ⁇ -opioid receptor at a concentration of the test substances of 1 ⁇ mol / l is determined and stated as percent inhibition of the specific binding.
  • rat mammalian synaptosomes are freshly isolated as described in the publication " The isolation of nerve endings from brain "by EG Gray and VP Whittaker, J. Anatomy 96, pages 79-88, 1962 , described. The corresponding literature description is hereby incorporated by reference and is considered part of the disclosure.
  • tissue hypothalamus for the determination of norepinephrine uptake inhibition and mark and pons for the determination of 5HT-uptake inhibition
  • tissue is suspended in ice-cooled 0.32 M sucrose (100 mg tissue / 1 mL) in a glass homogenizer with Teflon pestle Homogenized using five full up and downs at 840 rpm.
  • the homogenate is centrifuged at 4 ° C for 10 minutes at 1000 g. After subsequent centrifugation at 17000 g for 55 minutes, the synaptosomes (P 2 fraction) are obtained, which are resuspended in 0.32 M glucose (0.5 mU 100 mg of the original weight).
  • the respective uptake is measured in a 96-well microtiter plate.
  • the volume is 250 ⁇ l and the incubation is carried out at room temperature (about 20-25 ° C) under O 2 atmosphere.
  • the incubation time is 7.5 minutes for [ 3 H] -NA and 5 minutes for [ 3 H] -5-HT.
  • the 96 samples are filtered through a Unifilter GF / B ® microtiter plate (Packard) and incubated with 200 mL buffer using a washed "Brabdel Cell Harvester MPXRI-96T".
  • the Unifilter GF / B plate is dried at 55 ° C for 1 hour. Subsequently, the plate is sealed with a back seal ® (Packard) with 35 ul scintillation fluid per well (Ultima Gold ®, Packard) was added. After sealing with a top seal ® (Packard), the radioactivity in a "Trilux 1450 Microbeta" (Wallac, Freiburg, Germany), after adjustment of the equilibrium (around 5 hours), determined.
  • the amount of the protein used in the above determination corresponds to the values known from the literature, such as in " Protein measurement with the folinophenol reagent ", Lowry et al., J. Biol. Chem., 193, 265-275, 1951 described.
  • the binding site 2 of the sodium channel is the so-called batrachotoxin (BTX) binding site.
  • the ligand used is [ 3 H] -batrachotoxin A20 ⁇ -benzoate (10 nM in the reaction mixture).
  • the ion channel particles are enriched from the rat cerebrocortex, as in the publication of Gray and Whittaker, 1962, J. Anat. 76, 79-88 described. The corresponding description is hereby incorporated by reference and is considered part of the present disclosure.
  • Unspecific binding is defined as the radioactivity which is measured in the presence of veratridine (3 ⁇ 10 -4 M in the reaction).
  • the total batch is reduced to 250 .mu.l, so that the assay can be carried out on 96-well microtiter plates.
  • the incubation time in these microtiter plates is two hours at room temperature (about 20-25 ° C).
  • ether means diethyl ether, "EE” ethyl acetate, “DCM” dichloromethane, “DMF” dimethylformamide, “DME” dimethoxyethane “DMSO” dimethyl sulfoxide and “THF” tetrahydrofuran.
  • equivalents means equivalent molar amounts, “m.p.” Melting point or melting range, “Zers.” Decomposition, “RT” room temperature, “abs.” absolute (anhydrous),, “rac.” racemic, “conc.” concentrated, “min” minutes, “h” hours, “d” days, “vol.%” volume percent, “m%” mass percent and “M” is a concentration in mol / l.
  • the chemicals and solvents used were purchased commercially from conventional suppliers (for example, Acros, Acocado, Aldrich, Bachem, Fluka, Lancaster, Maybridge, Merck, Sigma, Tci, etc.) or synthesized by conventional methods known to those skilled in the art.
  • the stationary phase used for the column chromatography was silica gel 60 (0.040-0.063 mm) from E. Merck, Darmstadt.
  • Run Mixture ratios for chromatographic analyzes are always given in volume / volume.
  • decan-2-one 300mg, 0.8mmol was dissolved in ethyl methyl ketone (2 ml), water (8 ⁇ l) and TMSCI (106 ⁇ l) added and stirred overnight. The solid was filtered off and dried in vacuo.
  • decan-2-one 140 mg, 0.4 mmol was dissolved in ethyl methyl ketone ( 1 ml), treated with water (4 .mu.l) and TMSCI (59 .mu.l) and stirred overnight. The solid was filtered off and dried in vacuo.
  • Example 17 3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-methoxybenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one
  • Example 28 3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride
  • Example 29 1,3- ( S, R ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride
  • 1,3- ( S, R ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (370 mg, 0.8 mmol) was dissolved in ethyl methyl ketone ( 3 ml), treated with water (8 .mu.l) and TMSCI (109 .mu.l) and stirred overnight. The precipitated solid was filtered off and dried in vacuo. The product 1,3- ( S, R ) -dibenzyl-8- (4-chlorobenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 355 mg (89 %).
  • Example 22 1,3- ( S, R ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one
  • decan-2-one (230mg, 0.6 mmol) was dissolved in ethyl methyl ketone (2 ml), water (5 ⁇ l) and TMSCI (77 ⁇ l) added and stirred overnight. Then hexane (8 ml) was added, the aqueous phase separated and the residue dried in vacuo.
  • Examples 35 and 36 were prepared under microwave irradiation:
  • Example 36 1-Benzyl-8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride
  • 1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one 400mg, 1.2mmol was dissolved in ethyl methyl ketone (3mL), water (12 ⁇ l) and with TMSCI (166 ⁇ l) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained with a yield of 315 mg (71%).
  • Example 48 1,3- ( S ) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one
  • Example 50 1,3- ( S ) -dibenzyl-8- (4-fluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one
  • 1,3- ( S ) -Dibenzyl-8-butyryl-1,4,8-triaza-spiro [4.5] decan-2-one (272 mg, 0.7 mmol) was dissolved in ethyl methyl ketone (2.2 mL), washed with water ( 7 ⁇ l) and TMSCI (93 ⁇ l) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8-butyryl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 281 mg (95%) yield.
  • the product was the product 11,3- ( S ) -dibenzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride in a yield of 396 mg (93%).
  • Example 54 1,3- ( S ) -dibenzyl-8- (2,3-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride
  • 1,3- ( S ) -Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro [4.5] decan-2-one 450 mg, 0.8 mmol
  • ethyl methyl ketone 3.6 mL
  • TMSCI 118 ⁇ l
  • ether 10 ml
  • the solid was filtered off, washed with ether and dried in vacuo.
  • the product 1,3- ( S ) -dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in a yield of 402 mg (84%).
  • 1,3- ( S ) -dibenzyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one (410 mg, 0.9 mmol) was dissolved in ethyl methyl ketone (3.3 mL ), water (9 ⁇ l), TMSCl (121 ⁇ l), and ether (30 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product was obtained 1,3- ( S ) -dibenzyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride with a yield of 347 mg (79%).
  • Example 58 1,3- ( S ) -dibenzyl-8- (3-phenylpropionyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride
  • decan-2-one 400 mg, 0.8 mmol was dissolved in ethyl methyl ketone (3.2 mL dissolved, added with water (8 .mu.l), TMSCI (114 .mu.l) and with ether (20 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo.
  • 1,3- ( S ) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one (365 mg, 0.9 mmol) was dissolved in ethyl methyl ketone (2.9 ml dissolved, added with water (8 .mu.l), TMSCI (118 .mu.l) and with ether (20 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- (S) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 338 mg (85 %).
  • 1,3- ( S ) -dibenzyl-8- (3-methoxybenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (404 mg, 0.9 mmol) was dissolved in ethyl methyl ketone (3.2 mL ), with water (9 ⁇ l) and TMSCI (120 ul) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8- (3-methoxybenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 358 mg (82 %).
  • Example 62 1,3- ( S ) -dibenzyl-8- (4-fluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride
  • the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the above-indicated general formula I according to the invention exhibit good to very good inhibition of norepinephrine reuptake and good to very good inhibition of 5-hydroxytryptophan resumption.
  • the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I according to the invention exhibit pronounced analgesic activity.
  • these compounds of the invention also show excellent affinities for opioid receptors, in particular for the ⁇ -opioid receptor and / or for the batrachotoxin (BTX) binding site of the sodium channel.

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Abstract

Novel 1,4,8-triazaspiro[4,5]decan-2-one compounds corresponding to formula I processes for the preparation thereof, related methods of treatment and pharmaceutical formulations containing such compounds.

Description

Die vorliegende Erfindung betrifft substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen, Verfahren zu deren Herstellung, Arzneimittel enthaltend diese Verbindung sowie die Verwendung dieser Verbindungen zur Herstellung von Arzneimitteln.The present invention relates to substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds, processes for their preparation, medicaments containing this compound and the use of these compounds for the preparation of medicaments.

Fettsucht und daraus resultierende Störungen und Erkrankungen wie beispielsweise Herzerkrankungen stellen ein ernstzunehmendes und stetig wachsendes Problem für die Gesundheit großer Bevölkerungsgruppen, insbesondere in den hochentwickelten Industrienationen dar. Neben weiteren Einflußfaktoren wie Bewegungsmangel und ungesunder Ernährung beeinflußt auch die Hemmung der 5-Hydroxy-tryptophan-(Serotonin) Serotonin-Wiederaufnahme die Entstehung und den Verlauf dieser Krankheit. Es besteht daher ein großer Bedarf an geeigneten pharmakologischen Wirkstoffen, die die 5-Hydroxy-tryptophan- (Serotonin) Serotonin-Wiederaufnahme hemmen und sich daher insbesondere zur Therapie von Fettsucht eignen. Aus JP 01 207291 A und Y. Ishihara et al. (Chem. Pharm. Bull. 1992, 40 (5): 1177-1185 ) sind substituierte Triazaspirodecanon-Verbindungen bekannt, die pharmakologisch aktiv sind.Obesity and the resulting disorders and diseases such as heart disease represent a serious and growing problem for the health of large populations, especially in the highly developed industrial nations. In addition to other factors such as lack of exercise and unhealthy diet, the inhibition of 5-hydroxy-tryptophan ( Serotonin) serotonin reuptake the origin and course of this disease. There is therefore a great need for suitable pharmacological agents which inhibit the 5-hydroxy-tryptophan (serotonin) serotonin reuptake and are therefore particularly suitable for the treatment of obesity. Out JP 01 207291 A and Y. Ishihara et al. (Chem. Pharm. Bull. 1992, 40 (5): 1177-1185 ) are known substituted triazaspirodecanone compounds which are pharmacologically active.

Eine Aufgabe der vorliegenden Erfindung bestand daher darin, Verbindungen zur Verfügung zu stellen, die sich insbesondere als pharmazeutische Wirkstoffe in Arzneimitteln, bevorzugt in Arzneimitteln zur Prophylaxe und/oder Behandlung von Fettsucht, eignen.An object of the present invention was therefore to provide compounds which are particularly suitable as pharmaceutical active ingredients in medicaments, preferably in medicaments for the prophylaxis and / or treatment of obesity.

Es wurde nun überraschenderweise gefunden, daß die substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der nachstehend angegebenen allgemeinen Formel I sich nicht nur zur Regulation, vorzugsweise zur Inhibierung, der Serotonin (5-Hydroxytryptophan)-Wiederaufnahme und/oder zur Regulation, vorzugsweise zur Inhibierung, der Noradrenalin-Wiederaufnahme eignen, sondern darüber hinaus auch eine hohe Affinität für Opioid-Rezeptoren, insbesondere für µ-Opioid-Rezeptoren sowie für Batrachotoxin-(BTX)-Rezeptoren aufweisen und sich daher insbesondere als pharmazeutische Wirkstoffe in Arzneimitteln zur Prophylaxe und/oder Behandlung von mit diesen Rezeptoren bzw. Prozessen in Verbindung stehenden Erkrankungen eignenIt has now surprisingly been found that the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of general formula I given below are not only for the regulation, preferably for the inhibition, of serotonin (5-hydroxytryptophan) - Recovery and / or regulation, preferably for inhibition, the norepinephrine reuptake are suitable, but also have a high affinity for opioid receptors, in particular for μ-opioid receptors and for batrachotoxin (BTX) receptors and therefore in particular as pharmaceutical active ingredients in medicaments for prophylaxis and / or treatment of disorders associated with these receptors or processes

Ein Gegenstand der vorliegenden Erfindung sind daher substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der allgemeinen Formel I,

Figure imgb0001
worin
R1 für einen Wasserstoff-Rest, für einen linearen oder verzweigten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden unsubstituierten Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkinyl-Rest, für einen unsubstituierten oder wenigstens einfach substituierten Aryl- oder Heteroaryl-Rest, der über eine lineare oder verzweigte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende Alkylen-Gruppe gebunden ist, für einen über eine lineare oder verzweigte Alkylen-Gruppe gebundenen -C(=O)-OR5-Rest oder für einen über eine lineare oder verzweigte Alkylen-Gruppe gebundenen -O-(C=O)-R6-Rest steht,
R2 für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkinyl-Rest, oder für einen unsubstituierten oder wenigstens einfach substituierten Aryl- oder Heteroaryl-Rest steht, der über eine lineare oder verzweigte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende Alkylen-Gruppe gebunden sein kann,
R3 für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkinyl-Rest, für einen unsubstituierten oder wenigstens einfach substituierten Aryl- oder Heteroaryl-Rest, der über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende Alkylen-Gruppe gebunden und gegebenenfalls mit einem unsubstituierten oder wenigstens einfach substituierten monozyklischen Ringsystem kondensiert ist, für einen unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Ringglied aufweisenden, ggf. über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende Alkylen-Gruppe gebundenen cycloaliphatischen Rest, der mit einer linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkylen-Gruppe überbrückt und/oder mit einem unsubstituierten oder wenigstens einfach substituierten monozyklischen Ringsystem kondensiert sein kann, oder für eine - C(=O)-R4-Gruppe steht,
R4 für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden Alkinyl-Rest,
für einen unsubstituierten oder wenigstens einfach substituierten Aryl- oder Heteroaryl-Rest, der über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende Alkylen-, Alkenylen- oder Alkinylen-Gruppe gebunden und/oder mit einem unsubstituierten oder wenigstens einfach substituierten monozyklischen Ringsystem kondensiert sein kann,
für einen unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Ringglied aufweisenden, ggf. über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende Alkylen-Gruppe gebundenen cycloaliphatischen Rest, der mit einer linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten Alkylen-Gruppe wenigstens einfach überbrückt und/oder mit einem unsubstituierten oder wenigstens einfach substituierten monozyklischen Ringsystem kondensiert sein kann,
für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte Alkylen-Gruppe gebundenen -C(=O)-OR7-Rest, für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte Alkylen-Gruppe gebundenen -O-(C=O)-R8-Rest oder für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte Alkylen-Gruppe gebundenen -(C=O)-R9-Rest steht,
R5 und R6, unabhängig voneinander, jeweils für einen linearen oder verzweigten Alkyl-Rest, für einen linearen oder verzweigten Alkenyl-Rest oder für einen linearen oder verzweigten Alkinyl-Rest stehen,
R7 und R8, unabhängig voneinander, jeweils für einen Wasserstoff-Rest, für einen linearen oder verzweigten Alkyl-Rest, für einen linearen oder verzweigten Alkenyl-Rest, für einen linearen oder verzweigten Alkinyl-Rest, oder für einen unsubstituierten oder wenigstens einfach substituierten Aryl- oder Heteroaryl-Rest stehen,
R9 für einen linearen oder verzweigten Alkyl-Rest, für einen linearen oder verzweigten Alkenyl-Rest oder für einen linearen oder verzweigten Alkinyl-Rest steht,
jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastemomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, Insbesondere der Enantiomeren und/oder Diastereomeren, in einem beilebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, oder jeweils In Form entsprechender Solvate.An object of the present invention are therefore substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of general formula I,
Figure imgb0001
 wherein
R 1 is a hydrogen radical, a linear or branched, optionally at least one heteroatom as a chain member unsubstituted alkyl radical, a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having alkenyl radical , for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member alkynyl radical, an unsubstituted or at least monosubstituted aryl or heteroaryl radical having a linear or branched, optionally at least one Heteroatom as a chain-containing alkylene group is bound to a bonded via a linear or branched alkylene group -C (= O) -OR 5 radical or bonded via a linear or branched alkylene group -O- (C = O) -R 6 radical,
R 2 is a hydrogen radical, a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom chain member having alkyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as Chain link exhibiting alkenyl radical, a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having alkynyl radical, or an unsubstituted or at least monosubstituted aryl or heteroaryl radical which may be bound via a linear or branched, optionally at least one heteroatom as a chain member having alkylene group,
R 3 is a hydrogen radical, a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom chain member having alkyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as Chain link exhibiting alkenyl radical, a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom chain member having alkynyl radical, an unsubstituted or at least monosubstituted aryl or heteroaryl radical having a linear or branched , unsubstituted or at least monosubstituted, optionally containing at least one heteroatom as a chain member bound alkylene group and optionally with an unsubstituted or at least monosubstituted monocyclic ring system is condensed, for an unsubstituted or at least monosubstituted erten, optionally at least one heteroatom ring member having, optionally via a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having alkylene group bonded cycloaliphatic radical having a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having alkylene group bridged and / or may be condensed with an unsubstituted or at least monosubstituted monocyclic ring system, or represents a - C (= O) -R 4 group,
R 4 is a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom chain member having alkyl radical, a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having alkenyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member alkynyl radical,
for an unsubstituted or at least monosubstituted aryl or heteroaryl radical which is attached via a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as chain member having alkylene, alkenylene or alkynylene group and / or with a may be condensed unsubstituted or at least monosubstituted monocyclic ring system,
for an unsubstituted or at least monosubstituted, optionally at least one heteroatom ring member having, optionally via a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having alkylene group bonded cycloaliphatic radical having a linear or branched, unsubstituted or at least monosubstituted alkylene group may be at least simply bridged and / or condensed with an unsubstituted or at least monosubstituted monocyclic ring system,
for a -C (OO) -OR 7 radical bonded via a linear or branched, unsubstituted or at least monosubstituted alkylene group, for an -O- which is bonded via a linear or branched, unsubstituted or at least monosubstituted alkylene group C = O) -R 8 radical or is a (C = O) -R 9 radical attached via a linear or branched, unsubstituted or at least monosubstituted alkylene group,
R 5 and R 6 , independently of one another, are each a linear or branched alkyl radical, a linear or branched alkenyl radical or a linear or branched alkynyl radical,
R 7 and R 8 , independently of one another, each represent a hydrogen radical, a linear or branched alkyl radical, a linear or branched alkenyl radical, a linear or branched alkynyl radical, or an unsubstituted or at least simple substituted aryl or heteroaryl radical,
R 9 is a linear or branched alkyl radical, a linear or branched alkenyl radical or a linear or branched alkynyl radical,
in each case optionally in the form of one of its pure stereoisomers, in particular enantiomers or diastemomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in a casual mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Sofern einer der Reste R1 bis R9 für einen Alkyl-, Alkenyl- oder Alkinyl-Rest steht oder einen solchen Rest aufweist, kann dieser Rest - sofern nicht anders angegeben - unsubstituiert oder einfach oder mehrfach substituiert sein, vorzugsweise mit 1, 2, 3, 4 oder 5 Substituenten substituiert sein, wobei die Substituenten Jeweils unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus F, Cl, Br, I, C1-6-Alkoxy, -NO2, -OH, -SH, -(C=O)-OH, -(C=O)-O-C1-4-Alkyl, -Q-(C=O)-C1-4-Alkyl, -CH2-O-CH2-Phenyl, -CN, -CF3, -CHF2, -CH2F. unsubstituiertem Phenyl und -NRaRb, worin Ra und Rb jeweils unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus H, Methyl, Ethyl, n-Propyl, iso-Propyl, n-Butyl, sec-Butyl, tert.-Butyl, -(C=O)-O-C1-4-Alkyl und unsubstituiertem Phenyl. Alkenyl-Reste weisen wenigstens eine C-C-Doppelbindung und Alkinyl-Reste wenigstens eine C-C-Dreifachbindung auf.If one of the radicals R 1 to R 9 is an alkyl, alkenyl or alkynyl radical or has such a radical, this radical can-unless stated otherwise-be unsubstituted or monosubstituted or polysubstituted, preferably with 1, 2, Be substituted 3, 4 or 5 substituents, wherein the substituents can each be independently selected from the group consisting of F, Cl, Br, I, C 1-6 alkoxy, -NO 2 , -OH, -SH, - ( C = O) -OH, - (C = O) -OC 1-4 -alkyl, -Q- (C = O) -C 1-4 -alkyl, -CH 2 -O-CH 2 -phenyl, -CN , -CF 3, -CHF 2 , -CH 2 F. unsubstituted phenyl and -NR a R b , wherein R a and R b can each independently be selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert -butyl, - (C = O) -OC 1-4 -alkyl and unsubstituted phenyl. Alkenyl radicals have at least one C-C double bond and alkynyl radicals have at least one C-C triple bond.

Geeignete Alkyl-, Alkenyl- und Alkinyl-Reste, die einfach oder mehrfach substituiert sein können, können beispielsweise ausgewählt werden aus der Gruppe bestehend aus Methyl, Ethyl, n-Propyl, Isopropyl, n-Butyl, Isobutyl, sec-Butyl, tert-Butyl, n-Pentyl, iso-Pentyl, neo-Pentyl, sec-Pentyl, 2,2-Dimethyl-propyl, 1-Methyl-butyl, 1-Ethyl-propyl, 1-Propyl-butyl, 1-Ethyl-pentyl, Penta-1,3-dienyl, n-Hexyl, 2-Hexyl, n-Heptyl, n-Octyl, n-Nonyl, n-Decyl, -(CH2)-(CH)(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), Vinyl, Ethinyl, Propenyl, Alkyl, Propinyl, 1-Propinyl, 2-Propinyl, Butenyl, 1-Propenyl, 2-Propenyl, 1-Butenyl, 2-Butenyl, 3-Butenyl, 2-Methyl-2-butenyl, Butinyl, 1-Butinyl, 2-Butinyl, 3-Butinyl, Pentenyl, Pentinyl, Hexenyl und Hexinyl.Suitable alkyl, alkenyl and alkynyl radicals which may be monosubstituted or polysubstituted may be selected, for example, from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl Butyl, n-pentyl, iso-pentyl, neo-pentyl, sec-pentyl, 2,2-dimethyl-propyl, 1-methyl-butyl, 1-ethyl-propyl, 1-propyl-butyl, 1-ethyl-pentyl, Penta-1,3-dienyl, n-hexyl, 2-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, - (CH 2 ) - (CH) (C 2 H 5 ) - (CH 2 ) - (CH 2 ) - (CH 2 ) - (CH 3 ), vinyl, ethynyl, propenyl, alkyl, propynyl, 1-propynyl, 2-propynyl, butenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, butynyl, 1-butynyl, 2-butynyl, 3-butynyl, pentenyl, pentynyl, hexenyl and hexynyl.

Die erfindungsgemäß vorliegenden Alkyl-, Alkenyl- und Alkinyl-Reste könnensofern nicht anders angegeben - auch eines oder mehrere Heteroatome, vorzugsweise eines oder mehrere Sauerstoffatome und/oder eines oder mehrere Schwefelatome, besonders bevorzugt 1 oder 2 Sauerstoffatome und/oder 1 oder 2 Schwefelatome, als Kettenglied(er) aufweisen. Vorzugsweise befinden sich diese Heteroatome in einer nicht-endständigen Position des Jeweiligen Restes. Beispielhaft seien Reste wie -CH2-CH2-S-CH3, -CH2-O-CH2-CH2-O-CH3 oder -CH2-CH2-O-CH3 genannt.Unless otherwise stated, the alkyl, alkenyl and alkynyl radicals present in accordance with the invention may also contain one or more heteroatoms, preferably one or more oxygen atoms and / or one or more sulfur atoms, more preferably 1 or 2 oxygen atoms and / or 1 or 2 sulfur atoms, as chain link (s). Preferably, these heteroatoms are in a non-terminal position of the respective moiety. By way of example, radicals such as -CH 2 -CH 2 -S-CH 3 , -CH 2 -O-CH 2 -CH 2 -O-CH 3 or -CH 2 -CH 2 -O-CH 3 may be mentioned .

Sofern einer der Reste R3 oder R4 für einen cycloaliphatischen Rest steht oder einen cycloaliphatischen Rest aufweist, kann dieser Rest- sofern nicht anders angegebenunsubstituiert oder einfach oder mehrfach substituiert sein, vorzugsweise mit 1, 2, 3, 4 oder 5 Substituenten substituiert sein, wobei die Substituenten jeweils unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus F, Cl, Br, C1-6-Alkoxy, Oxo, C1-6-Alkyl, Hydroxy, -CN, -CF3, -CHF2, CH2F, unsubstituiertem Phenyl, -NRaRb, worin Ra und Rb jeweils unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus H, Methyl, Ethyl, n-Propyl, iso-Propyl und unsubstituiertem Phenyl, Thioxo (=S), I, -SF5, -NO2, -O-CF3,-S-CF3, -SH, -S-C1-5-Alkyl, -C(=O)-H, -C(=O)-C1-5-Alkyl, -C(=O)-OH, -C(=O)-O-C1-5-Alkyl, -(CH2)-C(=O)-OH, -(CH2)-C(=O)-O-C1-5-Alkyl, -(CH2)-Benzo[b]furanyl, -O-Phenyl, -O-Benzyl, Phenyl, Benzyl, Naphthyl und -(CH2)-Naphthyl, wobei Jeweils der zyklische Teil der Reste -O-Phenyl, -O-Benzyl, Phenyl, -(CH2)-Benzo[b]furanyl, Benzyl, Naphthyl und -(CH2)-Naphthyl mit 1, 2, 3, 4 oder 5 Substituenten unabhängig voneinander ausgewählt aus der Gruppe bestehend aus F, Cl, Br, -OH,-CF3, -SF5, -CN, -NO2, -O-C1-5-Alkyl, -C1-5-Alkyl, -O-CF3, -S-CF3, Phenyl und -O-Benzyl substituiert sein kann.If one of the radicals R 3 or R 4 is a cycloaliphatic radical or has a cycloaliphatic radical, this radical may, unless stated otherwise, be unsubstituted or monosubstituted or polysubstituted, preferably substituted by 1, 2, 3, 4 or 5 substituents, wherein each of the substituents may be independently selected from the group consisting of F, Cl, Br, C 1-6 alkoxy, oxo, C 1-6 alkyl, hydroxy, -CN, -CF 3 , -CHF 2 , CH 2 F, unsubstituted phenyl, -NR a R b , wherein R a and R b can each be independently selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl and unsubstituted phenyl, thioxo (= S ), I, -SF 5 , -NO 2 , -O-CF 3 , -S-CF 3 , -SH, -SC 1-5 -alkyl, -C (= O) -H, -C (= O) -C 1-5 alkyl, -C (= O) -OH, -C (= O) -OC 1-5 alkyl, - (CH 2 ) -C (= O) -OH, - (CH 2 ) -C (= O) -OC 1-5 alkyl, - (CH 2 ) benzo [b] furanyl, -O-phenyl, -O-benzyl, phenyl, benzyl, naphthyl and - (CH 2 ) naphthyl, In each case the cyclic part of the radicals -O-phenyl, -O-benzyl, phenyl, - (CH 2 ) -benzo [b] furanyl, benzyl, naphthyl and - (CH 2 ) -naphthyl with 1, 2, 3, 4 or 5 Substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF 5 , -CN, -NO 2 , -OC 1-5 -alkyl, -C 1-5 -alkyl, -O -CF 3 , -S-CF 3 , phenyl and -O-benzyl.

Unter cycloallphatischen Resten werden im Sinne der vorliegenden Erfindung sowohl gesättigte als auch ungesättigte Reste verstanden. Die cycloaliphatischen Reste können ggf. eines oder mehrere Heteroatome, vorzugsweise 1, 2, 3, 4 oder 5 Heteroatome unabhängig voneinander ausgewählt aus der Gruppe bestehend aus Stickstoff, Sauerstoff und Schwefel, als Ringglieder aufweisen.For the purposes of the present invention, cycloaliphatic radicals are understood as meaning both saturated and unsaturated radicals. The cycloaliphatic radicals may optionally have one or more heteroatoms, preferably 1, 2, 3, 4 or 5 heteroatoms independently selected from the group consisting of nitrogen, oxygen and sulfur, as ring members.

Geeignete cycloaliphatische Reste, die einfach oder mehrfach substituiert sein können, können beispielsweise ausgewählt werden aus der Gruppe bestehend aus Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Cycloheptyl, Cyclooctyl, Cyclopentenyl, Cyclohexenyl, Cycloheptenyl, Cyclooctenyl, Imidazolidinyl, Tetrahydrofuryl, Tetrahydrothiophenyl, Pyrrolidinyl, Piperidinyl, Morpholinyl, Piperazinyl, Thiomorpholinyl, Tetrahydropyranyl, Azepanyl, Diazepanyl und Dithiolanyl.Suitable cycloaliphatic radicals which may be monosubstituted or polysubstituted may be selected, for example, from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl , Morpholinyl, piperazinyl, thiomorpholinyl, tetrahydropyranyl, azepanyl, diazepanyl and dithiolanyl.

Die cycloaliphatischen Reste können ferner wenigstens einfach mit einer linearen oder verzweigten Alkylen-Gruppe überbrückt sein, vorzugsweise mit ein oder zwei linearen oder verzweigten C1-5-Alkylen-Gruppen überbrückt sein. Als Beispiele für derartige cycloaliphatischen Reste seien der 4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo-[2.2.1]-heptyl- bzw. der Adamantyl-Rest genannt.The cycloaliphatic radicals can further be at least singly bridged by a linear or branched alkylene group, preferably bridged by one or two linear or branched C 1-5 alkylene groups. Examples of such cycloaliphatic radicals are the 4,7,7-trimethyl-3-oxo-2-oxa-bicyclo [2.2.1] heptyl or adamantyl radical mentioned.

Sofern einer der Reste R1-R4, R7 und R8 für einen Aryl- oder Heteroaryl-Rest steht oder einen Aryl- oder Heteroaryl-Rest aufweist, kann dieser Aryl- oder Heteroaryl-Rest - sofern nicht anders angegeben - einfach oder mehrfach substituiert sein, vorzugsweise mit 1, 2, 3, 4 oder 5 Substituenten substiuiert sein, wobei die Substituenten jeweils unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus F, Cl, Br, I, -CN, -NO2, C1-5-Alkyl, OH, SH, C1-5-Alkoxy, C1-5-Perfluoroalkoxy, -C(=O)-C1-5-Alkyl, -C(=O)-O-C1-5-Alkyl, -(CH2)1-3-O-(C=O)-Phenyl, -S-C1-5-Alkyl, -S(=O)2-C1-6-alkyl, -S(=O)2-NH2, -NH-(C=O)-CH3, -S-CHF2, -S-CH2F, -C(=O)- C1-5-Perfluoroalkyl, -CF3, CHF2, CH2F. Phenyl, Phenoxy und -NRaRb, worin Ra und Rb jeweils unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus H, Methyl, Ethyl, n-Propyl, iso-Propyl und unsubstituiertem Phenyl, -SF5, -O-C2-5-Alkenyl, -O-CF3, -O-CHF2, -O-CH2F, -C(=O)-OH, -O-C(=O)-C1-5-Alkyl, -O-C(=O)-Phenyl, -(CH2)-O-C(=O)-C1-5-Alkyl, -NH-C1-5-Alkyl, -N(C1-5-Alkyl)2, -NH-C(=O)-O-C1-5-Alkyl, -C(=O)-H, -C(=O)-C1-5-Alkyl, -C(=O)-NH2, -C(=O)-NH-C1-5-Alkyl, C(=O)-N-(C1-5-Alkyl)2, -S(=O)2-NH-C1-5-Alkyl, -S(=O)2-NH-Phenyl, -(CH2)-Benzo[b]furanyl, -O-Phenyl, -S-Phenyl, -S-Benzyl, -O-Benzyl, Phenyl und Benzyl.
Der zyklische Teil der Reste -S(=O)2-NH-Phenyl, -O-Phenyl, -S-Phenyl, -S-Benzyl, - O-Benzyl, Phenyl, -(CH2)-Benzo[b]furanyl und Benzyl kann mit 1, 2, 3, 4 oder 5 Substituenten unabhängig voneinander ausgewählt aus der Gruppe bestehend aus F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-C1-5-Alkyl, -C1-5-Alkyl, -O-CF3, -S-CF3, Phenyl und -O-Benzyl substituiert sein.
Die Phenyl- und Phenoxy-Substituenten können selbst einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, -S-CHF2, -CF3, -CHF2, -CH2F, -CN, -NO2, C1-5-Alkyl und C1-5-Alkoxy substituiert sein.If one of the radicals R 1 -R 4 , R 7 and R 8 is an aryl or heteroaryl radical or has an aryl or heteroaryl radical, this aryl or heteroaryl radical-unless stated otherwise-can be simple or be substituted several times, preferably be substiuiert with 1, 2, 3, 4 or 5 substituents, wherein the substituents can each be independently selected from the group consisting of F, Cl, Br, I, -CN, -NO 2 , C 1 -5- alkyl, OH, SH, C 1-5 -alkoxy, C 1-5 -perfluoroalkoxy, -C (= O) -C 1-5 -alkyl, -C (= O) -OC 1-5 -alkyl , - (CH 2 ) 1-3 -O- (C = O) -phenyl, -SC 1-5 -alkyl, -S (= O) 2 -C 1-6 -alkyl, -S (= O) 2 -NH 2 , -NH- (C =O) -CH 3 , -S-CHF 2 , -S-CH 2 F, -C (= O) -C 1-5 -perfluoroalkyl, -CF 3 , CHF 2 , CH 2 F. phenyl, phenoxy and -NR a R b , wherein each of R a and R b can be independently selected from the group consisting of H, methyl, ethyl, n-propyl, iso-propyl and unsubstituted phenyl, -SF 5 , -OC 2-5 alkenyl, -O-CF 3 , -O-CHF 2 , -O-C H 2 F, -C (= O) -OH, -OC (= O) -C 1-5 alkyl, -OC (= O) -phenyl, - (CH 2 ) -OC (= O) -C 1 -5- alkyl, -NH-C 1-5 -alkyl, -N (C 1-5 -alkyl) 2 , -NH-C (= O) -OC 1-5 -alkyl, -C (= O) - H, -C (= O) -C 1-5 -alkyl, -C (= O) -NH 2 , -C (= O) -NH-C 1-5 -alkyl, C (= O) -N- (C 1-5 alkyl) 2 , -S (= O) 2 -NH-C 1-5 alkyl, -S (= O) 2 -NH-phenyl, - (CH 2 ) benzo [b] furanyl , -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl.
The cyclic part of the radicals -S (= O) 2 -NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, - (CH 2 ) -benzo [b] furanyl and benzyl may be selected from the group consisting of 1, 2, 3, 4 or 5 substituents independently of one another F, Cl, Br, -OH, -CF 3 , -SF 5 , -CN, -NO 2 , -OC 1-5 alkyl, -C 1-5 alkyl, -O-CF 3 , -S-CF 3 , phenyl and -O-benzyl.
The phenyl and phenoxy substituents may themselves be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -S-CHF 2 , -CF 3 , -CHF 2 , -CH 2 F , -CN, -NO 2 , C 1-5 alkyl and C 1-5 alkoxy.

Die Heteroatome des Heteroaryl-Restes können bevorzugt ausgewählt werden aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel. Vorzugsweise konnen die Heteroaryl-Reste 1, 2, 3, 4 oder 5 Heteroatom(e) unabhängig voneinander ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel als Ringglied(er) aufweisen.The heteroatoms of the heteroaryl radical can preferably be selected from the group consisting of oxygen, nitrogen and sulfur. Preferably, the heteroaryl radicals may have 1, 2, 3, 4 or 5 heteroatom (s) independently selected from the group consisting of oxygen, nitrogen and sulfur as the ring member (s).

Geeignete Aryl-Reste können bevorzugt ausgewählt werden aus der Gruppe bestehend aus Phenyl-, 1-Naphthyl und 2-Naphthyl.Suitable aryl radicals may preferably be selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl.

Geeignete Heteroaryl-Reste können bevorzugt ausgewählt werden aus der Gruppe bestehend aus Pyrrolyl, Indolyl, Furyl (Furanyl), Benzofuranyl, Thienyl (Thiophenyl), Benzothienyl, Pyrazolyl, Imidazolyl, Thiazolyl, Thiadiazolyl, Triazolyl, Oxazolyl, Isoxazolyl, Pyridinyl, Pyridazinyl, Pyrimidinyl, Pyrazinyl, Pyranyl, Indazolyl, Purinyl, Indolizinyl, Chinolinyl, Isochinolinyl, Chinazolinyl, Carbazolyl, Phenazinyl, Phenothiazinyl und Oxadiazolyl, Benzo[1,3]dioxolyl, Benzo[1,2,5]oxadiazolyl und Chromanyl und Isoindolyl.Suitable heteroaryl radicals may preferably be selected from the group consisting of pyrrolyl, indolyl, furyl (furanyl), benzofuranyl, thienyl (thiophenyl), benzothienyl, pyrazolyl, imidazolyl, thiazolyl, thiadiazolyl, triazolyl, oxazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl , Pyrazinyl, pyranyl, indazolyl, purinyl, indolizinyl, quinolinyl, isoquinolinyl, quinazolinyl, carbazolyl, phenazinyl, phenothiazinyl and oxadiazolyl, benzo [1,3] dioxolyl, benzo [1,2,5] oxadiazolyl and chromanyl and isoindolyl.

Unter einem monozyklischen Ringsystem wird im Sinne der vorliegenden Erfindung ein monozyklischer Kohlenwasserstoffrest verstanden, der gesättigt, ungesättigt oder aromatisch sein und ggf. ein oder mehrere Heteroatome als Ringglieder aufweisen kann. Ein solches monozyklisches Ringsystem kann beispielsweise mit einem Aryl-Rest oder einem Heteroaryl-Rest kondensiert, d.h. anneliert bzw. verbunden sein.
Die Heteroatome eines solchen monozyklischen Ringsystems können jeweils bevorzugt ausgewählt werden aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel. Vorzugsweise kann der Ring des Ringsystems 1, 2, 3, 4 oder 5 Heteroatom(e) unabhängig voneinander ausgewählt aus der Gruppe bestehend aus Sauerstoff, Stickstoff und Schwefel als Ringglied(er) aufweisen.For the purposes of the present invention, a monocyclic ring system is understood as meaning a monocyclic hydrocarbon radical which may be saturated, unsaturated or aromatic and may optionally have one or more heteroatoms as ring members. Such a monocyclic ring system may, for example, be condensed with an aryl radical or a heteroaryl radical, ie be fused or bonded.
The heteroatoms of such a monocyclic ring system may each preferably be selected from the group consisting of oxygen, nitrogen and sulfur. Preferably, the ring of the ring system may have 1, 2, 3, 4 or 5 heteroatom (s) independently selected from the group consisting of oxygen, nitrogen and sulfur as the ring member (s).

Vorzugsweise ist der Ring des Ringsystems 5- oder 6-gliedrig oder 7-gliedrig. Das Ringsystem kann einfach oder mehrfach substituiert sein, vorzugsweiste mit 1, 2, 3, 4 oder 5 Substituenten substituiert sein, wobei die Substituenten ausgewählt werden können aus der Gruppe bestehend aus F, Cl, Br, I, -CN, -NO2, Oxo, C1-5-Alkyl, C1-6-Alkoxy, C1-5-Perfluoralkoxy, -C(=O)-C1-6-Alkyl, -C(=O)-O-C1-5-Alkyl, -S(=O)2-C1-6-alkyl, -C(=O)- C1-6-Perfluoroalkyl, -CF3, CHF2, CH2F und -NRaRb, worin Ra und Rb jeweils unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus H, Methyl, Ethyl, n-Propyl, iso-Propyl und unsubstituiertem Phenyl, Thioxo (=S), -SF5, -OH, -O-C2-5-Alkenyl, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-C1-5-Alkyl, -C(=O)-OH, -O-C(=O)-C1-5-Alkyl, -O-C(=O)-Phenyl, -(CH2)-O-C(=O)-C1-5-Alkyl, -(CH2)-O-C(=O)-Phenyl, -NH-C1-5-Alkyl, -N(C1-5-Alkyl)2, -NH-C(=O)-O-C1-5-Alkyl, -NH-C(=O)-C1-5-Alkyl, -C(=O)-H, - C(=O)-NH2, -C(=O)-NH-C1-5-Alkyl, C(=O)-N-(C1-5-Alkyl)2, -S(=O)2-NH2, -S(=O)2-NH-C1-5-Alkyl, -S(=O)2-NH-Phenyl, -(CH2)-Benzo[b]furanyl, -O-Phenyl, -S-Phenyl, -S-Benzyl, -O-Benzyl, Phenyl und Benzyl, wobei Jeweils der zyklische Teil der Reste -O-C(=O)-Phenyl, -(CH2)-O-C(=O)-Phenyl, -S(=O)2-NH-Phenyl, -O-Phenyl, -S-Phenyl, - S-Benzyl, -O-Benzyl, Phenyl, -(CH2)-Benzo[b]furanyl und Benzyl mit 1, 2, 3, 4 oder 5 Substituenten unabhängig voneinander ausgewählt aus der Gruppe bestehend aus F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-C1-5-Alkyl, -C1-5-Alkyl, -O-CF3, -S-CF3, Phenyl und -O-Benzyl substituiert sein kann.Preferably, the ring of the ring system is 5- or 6-membered or 7-membered. The ring system can be monosubstituted or polysubstituted, preferably with 1, 2, 3, 4 or 5 substituents, where the substituents can be selected from the group consisting of F, Cl, Br, I, -CN, -NO 2 , Oxo, C 1-5 alkyl, C 1-6 alkoxy, C 1-5 perfluoroalkoxy, -C (= O) -C 1-6 alkyl, -C (= O) -OC 1-5 alkyl , -S (= O) 2 -C 1-6 alkyl, -C (= O) -C 1-6 perfluoroalkyl, -CF 3 , CHF 2 , CH 2 F and -NR a R b , wherein R a and R b can each independently be selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl and unsubstituted phenyl, thioxo (= S), -SF 5 , -OH, -OC 2-5 - Alkenyl, -NH 2 , -NO 2 , -O-CF 3 , -O-CHF 2 , -O-CH 2 F, -S-CF 3 , -S-CHF 2 , -S-CH 2 F, -SH , -SC 1-5 -alkyl, -C (= O) -OH, -OC (= O) -C 1-5 -alkyl, -OC (= O) -phenyl, - (CH 2 ) -OC (= O) -C 1-5 -alkyl, - (CH 2 ) -OC (= O) -phenyl, -NH-C 1-5 -alkyl, -N (C 1-5 -alkyl) 2 , -NH-C (= O) -OC 1-5 -alkyl, -NH-C (= O) -C 1-5 -alkyl, -C (= O) -H, -C (= O) -NH 2 , -C ( = O) -NH-C 1-5 alkyl, C (= O) -N- (C 1-5- alkyl) 2 , -S (= O) 2 -NH 2 , -S (= O) 2 -NH-C 1-5 -alkyl, -S (= O) 2 -NH-phenyl, - ( CH 2 ) benzo [b] furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, where in each case the cyclic part of the radicals -OC (= O) -phenyl, - (CH 2 ) -OC (= O) -phenyl, -S (= O) 2 -NH-phenyl, -O-phenyl, -S-phenyl, - S-benzyl, -O-benzyl, phenyl, - ( CH 2 ) benzo [b] furanyl and benzyl having 1, 2, 3, 4 or 5 substituents independently of one another selected from the group consisting of F, Cl, Br, -OH, -CF 3 , -SF 5 , -CN, -NO 2 , -OC 1-5 alkyl, -C 1-5 alkyl, -O-CF 3 , -S-CF 3 , phenyl and -O-benzyl.

Weist einer der Reste R1-R4 eine lineare oder verzweigte Alkylen-, Alkenylen- oder Alkinylen-Gruppe auf, so kann diese - sofern nicht anders angegeben - unsubstituiert oder einfach oder mehrfach substituiert sein, vorzugsweise mit 1, 2, 3, 4 oder 5 Substituenten substituiert sein, wobei die Substituenten unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus F, Cl, Br, C1-6-Alkoxy, Hydroxy, CN, CF3, CHF2, CH2F, unsubstitulertem Phenyl und -NRaRb, worin Ra und Rb jeweils unabhängig voneinander ausgewählt werden können aus der Gruppe bestehend aus H, C1-3-Alkyl und unsubstituiertem Phenyl. Die Alkylen-Gruppe kann auch eines oder mehrere Heteroatome, vorzugsweise wenigstens ein Sauerstoffatom und/oder wenigstens ein Schwefelatom, besonders bevorzugt 1 oder 2 Sauerstoffatom(e) und/oder Schwefelatom(e), als Kettenglied(er) aufweisen. Eine Alkenylen-Gruppe weist wenigstens eine Kohlenstoff-Kohlenstoff-Doppelbindung, eine Alkinylen-Gruppe wenigstens eine Kohlenstoff-Kohlenstoff-Dreifachbindung auf.If one of the radicals R 1 -R 4 has a linear or branched alkylene, alkenylene or alkynylene group, this may-unless stated otherwise-be unsubstituted or monosubstituted or polysubstituted, preferably with 1, 2, 3, 4 or 5 substituents, wherein the substituents can be independently selected from the group consisting of F, Cl, Br, C 1-6 alkoxy, hydroxy, CN, CF 3 , CHF 2 , CH 2 F, unsubstitulertem phenyl and NR a R b , wherein each of R a and R b can be independently selected from the group consisting of H, C 1-3 alkyl and unsubstituted phenyl. The alkylene group may also have one or more heteroatoms, preferably at least one oxygen atom and / or at least one sulfur atom, more preferably 1 or 2 oxygen atom (s) and / or sulfur atom (s), as a chain member (s). An alkenylene group has at least one carbon-carbon double bond, an alkynylene group has at least one carbon-carbon triple bond.

Die jeweiligen Alkylen-, Alkenylen- oder Alkinylen- Gruppen können - sofern nicht anders angegeben - auch eines oder mehrere Heteroatome, vorzugsweise eines oder mehrere, beispielsweise 1 oder 2, Sauerstoffatome und/oder eines oder mehrere, beispielsweise 1 oder 2, Schwefelatome, als Kettenglied(er) aufweisen.The respective alkylene, alkenylene or alkynylene groups may, unless stated otherwise, also one or more heteroatoms, preferably one or more, for example 1 or 2, oxygen atoms and / or one or more, for example 1 or 2, sulfur atoms, as Chain link (he) have.

Beispielhaft seien Alkylen-Gruppen wie -(CH2)-, -(CH(CH3))-, -(CH2)2-, -(CH2)2-O-, -(CH2)3-, -(CH2)4-, -(CH2)5-, -(CH2)6-, -(CH2)7-, -(CH2)8-, -(CH2)9- und -(CH2)10-, Alkenylen-Gruppen wie -CH=CH- und Alkinylen-Gruppen wie -C≡C- genannt.Examples include alkylene groups such as - (CH 2) -, - (CH (CH 3)) -, - (CH 2) 2 -, - (CH 2) 2 -O-, - (CH 2) 3 -, - (CH 2 ) 4 -, - (CH 2 ) 5 -, - (CH 2 ) 6 -, - (CH 2 ) 7 -, - (CH 2 ) 8 -, - (CH 2 ) 9 - and - (CH 2 ) 10 -, alkenylene groups such as -CH = CH- and alkynylene groups such as -C≡C- called.

Bevorzugt sind substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I, in denen R1 für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C1-10-Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C2-10-Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C2-10-Alkinyl-Rest, für einen unsubstituierten oder wenigstens einfach substituierten, 5- bis 14-gliedrigen Aryl- oder Heteroaryl-Rest, der über eine lineare oder verzweigte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende C1-5-Alkylen-Gruppe gebunden ist, für einen über eine lineare oder verzweigte C1-5-Alkylen-Gruppe gebundenen -C(=O)-OR5-Rest oder für einen über eine lineare oder verzweigte C1-5-Alkylen-Gruppe gebundenen -O-C(=O)-R6-Rest steht,
vorzugsweise für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten C1-5-Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten C2-5-Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten C2-5-Alkinyl-Rest, für einen unsubstituierten oder wenigstens einfach substituierten Phenyl- oder Naphthyl-Rest, der über eine lineare oder verzweigte, ggf. eines oder mehrere Sauerstoffatome als Kettenglied aufweisende C1-5-Alkylen-Gruppe gebunden ist, für einen über eine lineare oder verzweigte C1-4-Alkylen-Gruppe gebundenen -C(=O)-OR5-Rest oder für einen über eine lineare oder verzweigte C1-4-Alkylen-Gruppe gebundenen -O-C(=O)-R6-Rest steht,
besonders bevorzugt für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten C1-4-Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten C2-5-Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten C2-3-Alkinyl-Rest, für einen Phenyl- oder Naphthyl-Rest, der über eine -(CH2)-, -(CH2)2-, -(CH2)3- oder -(CH2)2-O-Brücke gebunden und ggf. einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CN, NO2, C1-5-Alkyl, C1-5-Alkoxy, -C(=O)-C1-5-Alkyl, -C(=O)-O-C1-5-Alkyl, -S(=O)2-C1-6-alkyl, -C(=O)- C1-5-Perfluoroalkyl, -CF3, CHF2 und CH2F substituiert ist, für einen über eine -(CH2)-Gruppe gebundenen -C(=O)-OR5-Rest oder für einen über eine -(CH2)-, -(CH2)2-, -(CH2)3- oder -(CH2)4-Gruppe gebundenen -O-C(=O)-R6-Rest steht, und jeweils die übrigen Reste R2-R9 die vorstehend genannte Bedeutung haben, jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, oder jeweils in Form entsprechender Solvate.Preference is given to substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the abovementioned general formula I in which R 1 is a hydrogen radical, a linear or branched, unsubstituted, optionally at least one heteroatom C 1-10 -alkyl radical which has a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as chain link, C 2-10 -alkenyl radical, a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkynyl radical, an unsubstituted or at least monosubstituted, 5- to 14-membered aryl or heteroaryl radical which is a linear or branched, optionally at least one heteroatom as a chain member having C 1-5 alkylene group is bound for a via a linear or branched C 1-5 alkylene group bound -C (= O) -OR 5 - Is a radical or an -OC (OO) -R 6 radical bonded via a linear or branched C 1-5 -alkylene group,
preferably a hydrogen radical, a linear or branched, unsubstituted C 1-5 alkyl radical, a linear or branched, unsubstituted C 2-5 alkenyl radical, a linear or branched, unsubstituted C 2-5 Alkynyl radical, an unsubstituted or at least monosubstituted phenyl or naphthyl radical which is bonded via a linear or branched, optionally one or more oxygen atoms as a chain member having C 1-5 alkylene group, for one about a linear or branched C 1-4 -alkylene group bonded -C (= O) -OR 5 radical or is an -OC (OO) -R 6 radical attached via a linear or branched C 1-4 -alkylene group,
particularly preferably a hydrogen radical, a linear or branched, unsubstituted C 1-4 -alkyl radical, a linear or branched, unsubstituted C 2-5 -alkenyl radical, a linear or branched, unsubstituted C 2- 3- alkynyl radical, for a phenyl or naphthyl radical which has a - (CH 2 ) -, - (CH 2 ) 2 -, - (CH 2 ) 3 - or - (CH 2 ) 2 -O- Bound and optionally mono- or polysubstituted, identical or different, with a substituent selected from the group consisting of F, Cl, Br, CN, NO 2 , C 1-5 -alkyl, C 1-5 -alkoxy, -C ( = O) -C 1-5 alkyl, -C (= O) -OC 1-5 alkyl, -S (= O) 2 -C 1-6 alkyl, -C (= O) -C 1- 5 -perfluoroalkyl, -CF 3 , CHF 2 and CH 2 F is substituted for an attached via a - (CH 2 ) group -C (= O) -OR 5 radical or for a via a - (CH 2 ) -, - (CH 2 ) 2 -, - (CH 2 ) 3 - or - (CH 2 ) 4 group bonded -OC (= O) -R 6 radical, and in each case the remaining radicals R 2 -R 9 have the abovementioned meaning, in each case gg in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates ,

Weiterhin bevorzugt sind substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I, worin der Rest R2 für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C1-10-Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C2-10-Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C2-10-Alkinyl-Rest, oder für einen unsubstituierten oder wenigstens einfach substituierten, 5- bis 14-gliedrigen Aryl- oder Heteroaryl-Rest steht, der über eine lineare oder verzweigte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende C1-5-Alkylen-Gruppe gebunden sein kann,
vorzugsweise für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten, ggf. eines oder mehrere Sauerstoffatome und/oder eines oder mehrere Schwefelatome als Kettenglied aufweisenden C1-5-Alkyl-Rest oder für einen Phenyl- oder Naphthyl-Rest steht, der einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CN, NO2, C1-5-Alkyl, C1-5-Alkoxy, -C(=O)-C1-5-Alkyl, -C(=O)-O-C1-5-Alkyl,-S(=O)2-C1-6-alkyl, -C(=O)- C1-5-Perfluoroalkyl, -CF3, CHF2 und CH2F substituiert und/oder über eine -(CH2)-, -(CH2)2-, -(CH2)3- oder -(CH2)2-O-Brücke gebunden sein kann,
besonders bevorzugt für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten, ggf. eines oder mehrere Schwefelatome als Kettenglied aufweisenden C1-5-Alkyl-Rest oder für einen Phenyl-Rest steht, wobei der Phenyl-Rest einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CN, NO2, C1-5-Alkyl, C1-5-Alkoxy, -C(=O)-C1-5-Alkyl, -C(=O)-O-C1-5-Alkyl, -S(=O)2-C1-6-alkyl, -C(=O)-C1-5-Perfluoroalkyl, -CF3, CHF2 und CH2F substituiert und/oder über eine -(CH2)-Brücke gebunden sein kann, und jeweils die übrigen Reste R1 und R3 bis R9 die vorstehend genannte Bedeutung haben, jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, oder jeweils in Form entsprechender Solvate.Also preferred are substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I given above, wherein the radical R 2 is a hydrogen radical, a linear or branched, unsubstituted or at least monosubstituted , optionally at least one heteroatom as a chain member C 1-10 alkyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkenyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkynyl radical, or is an unsubstituted or at least monosubstituted, 5- to 14-membered aryl or heteroaryl radical which may be bonded via a linear or branched C 1-5 -alkylene group which may have at least one heteroatom as chain member,
is preferably a hydrogen radical, a linear or branched, unsubstituted, optionally one or more oxygen atoms and / or one or more sulfur atoms as a chain member having C 1-5 alkyl radical or a phenyl or naphthyl radical, which is monosubstituted or polysubstituted, identical or different, with a substituent selected from the group consisting of F, Cl, Br, CN, NO 2 , C 1-5 -alkyl, C 1-5 -alkoxy, -C (= O) - C 1-5 alkyl, -C (= O) -OC 1-5 alkyl, -S (= O) 2 -C 1-6 alkyl, -C (= O) -C 1-5 perfluoroalkyl, -CF 3 , CHF 2 and CH 2 F are substituted and / or bonded via a - (CH 2 ) -, - (CH 2 ) 2 -, - (CH 2 ) 3 - or - (CH 2 ) 2 -O-bridge can be,
particularly preferably represents a hydrogen radical, a linear or branched, unsubstituted, optionally one or more sulfur atoms as a chain member having C 1-5 alkyl radical or a phenyl radical, where the phenyl radical mono- or polysubstituted, identical or different, having one substituent selected from the group consisting of F, Cl, Br, CN, NO 2 , C 1-5 -alkyl, C 1-5 -alkoxy, -C (= O) -C 1-5 - Alkyl, -C (= O) -OC 1-5 alkyl, -S (= O) 2 -C 1-6 alkyl, -C (= O) -C 1-5 perfluoroalkyl, -CF 3 , CHF 2 and CH 2 F substituted and / or may be bonded via a - (CH 2 ) bridge, and in each case the remaining radicals R 1 and R 3 to R 9 have the abovementioned meaning, in each case optionally in the form of one of their pure stereoisomers , in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Des weiteren sind substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I bevorzugt, in denen R3 für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C1-10-Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C2-10-Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C2-10-Alkinyl-Rest, für einen unsubstituierten oder wenigstens einfach substituierten 5- bis 14-gliedrigen Aryl- oder Heteroaryl-Rest, der über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende C1-5-Alkylen-Gruppe gebunden und gegebenenfalls mit einem unsubstituierten oder wenigstens einfach substituierten monozyklischen Ringsystem kondensiert ist, für einen unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Ringglied aufweisenden C3-8-cycloaliphatischen Rest steht, der über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende C1-5-Alkylen-Gruppe gebunden und/oder mit einem unsubstituierten oder wenigstens einfach substituierten monozyklischen Ringsystem kondensiert sein kann, oder für eine -C(=O)-R4-Gruppe steht,
vorzugsweise für einen Wasserstoff-Rest, für einen Biphenyl-Rest, der über eine - (CH2)-, -(CH2)2- oder -(CH2)3-Brücke gebunden ist, oder für eine C(=O)-R4-Gruppe steht,
besonders bevorzugt für eine -C(=O)-R4-Gruppe steht, und jeweils die übrigen R1, R2 und R4 bis R9 die vorstehend genannte Bedeutung haben, jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, oder jeweils in Form entsprechender Solvate.Furthermore, substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the above-indicated general formula I are preferred in which R 3 is a hydrogen radical, a linear or branched, unsubstituted or at least monosubstituted , optionally at least one heteroatom as a chain member C 1-10 alkyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkenyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkynyl radical, an unsubstituted or at least monosubstituted 5- to 14-membered aryl or Heteroaryl radical which is attached via a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 1-5 alkylene group and optionally fused with an unsubstituted or at least monosubstituted monocyclic ring system, for a unsubstituted or at least monosubstituted, optionally at least one heteroatom as a ring member having C 3-8 cycloaliphatic radical which is a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 1-5 alkylene Group may be bonded and / or may be condensed with an unsubstituted or at least monosubstituted monocyclic ring system, or represents a -C (= O) -R 4 group,
preferably a hydrogen radical, a biphenyl radical bound via a - (CH 2 ) -, - (CH 2 ) 2 - or - (CH 2 ) 3 bridge, or a C (= O) R 4 group stands,
particularly preferred is a -C (= O) -R 4 group, and in each case the remaining R 1 , R 2 and R 4 to R 9 have the abovementioned meaning, in each case optionally in the form of one of their pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Weiterhin bevorzugt sind solche substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I, in denen der Rest R4
für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C1-10-Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C2-10-Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Kettenglied aufweisenden C2-10-Alkinyl-Rest,
für einen unsubstituierten oder wenigstens einfach substituierten 5- bis 14- gliedrigen Aryl- oder Heteroaryl-Rest, der über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende C1-5-Alkylen-, C2-5-Alkenylen oder C2-5-Alkinylen-Gruppe gebunden und/oder mit einem unsubstituierten oder wenigstens einfach substituierten monozyklischen Ringsystem kondensiert sein kann,
für einen unsubstituierten oder wenigstens einfach substituierten, ggf. wenigstens ein Heteroatom als Ringglied aufweisenden, ggf. über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte, ggf. wenigstens ein Heteroatom als Kettenglied aufweisende C1-6-Alkylen-Gruppe gebundenen C3-8 cycloaliphatischen Rest, der mit einer linearen oder verzweigten, unsubstituierten oder wenigstens einfach substituierten C1-6-Alkylen-Gruppe wenigstens einfach überbrückt und/oder mit einem unsubstituierten oder wenigstens einfach substituierten monozyklischen Ringsystem kondensiert sein kann,
für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte C1-5-Alkylen-Gruppe gebundenen -C(=O)-OR7-Rest, für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte C1-5-Alkylen-Gruppe gebundenen -O-(C=O)-R8-Rest oder für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte C1-5-Alkylen-Gruppe gebundenen -(C=O)-R9-Rest steht,
vorzugsweise für einen linearen oder verzweigten, ggf. eines oder mehrere Sauerstoffatome und/oder eines oder mehrere Schwefelatome als Kettenglied aufweisenden C1-10-Alkyl-Rest, der unsubstituiert oder wenigstens einfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus Phenyl, Di-(C1-5-Alkylamino), Carboxy und -NH-(C=O)-O-C1-5-Alkyl substituiert sein kann, für einen linearen oder verzweigten, unsubstituierten C2-5-Alkenyl-Rest, für einen Phenyl-Rest, Naphthyl-Rest, Furyl- (Furanyl-)-Rest, Thienyl-(Thiophenyl-)-Rest oder [1,2,3]-Triazolyl-Rest, Benzo[1.3]dioxolyl-Rest, Benzo[1,2,5]oxadiazolyl-Rest, Chromanyl-Rest, Pyrimidinyl-Rest, Pyrazolyl-Rest, Pyridinyl-Rest, Isoxazolyl-Rest oder [1,2,3]-Thiadiazolyl-Rest, wobei der zyklische Rest jeweils über eine -(CH2)-, - (CH2)-O-, -CH=CH-, -(CH2)2-, -(CH2)2-O-, oder -(CH2)3-Brücke gebunden sein kann und/oder einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, -CN, -NO2, C1-5-Alkyl, C1-5-Alkoxy, C1-5-Perfluoralkoxy, -C(=O)-C1-5-Alkyl, -C(=O)-O-C1-5-Alkyl, -(CH2)1-3-O-C(=O)-Phenyl, -N(CH3)2, -S(=O)2-C1-6-alkyl, -S(=O)2-NH2, -C(=O)-C1-5-Perfluoroalkyl, -S-C1-5-Alkyl, -S-CH2F, -S-CHF2, -SCF3, -CF3, -NH-(C=O)-CH3, -SO2-NH2, -CHF2, -CH2F, Phenyl und Phenoxy, wobei die letztgenannten Phenyl- und Phenoxy Substituenten selbst einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, -S-CHF2, -CF3, -CHF2, -CH2F, CN, N02, C1-5-Alkyl und C1-5-Alkoxy substituiert sein können,
für einen ggf. wenigstens ein Heteroatom als Ringglied aufweisenden, ggf. über eine -(CH2)-, -(CH2)2- oder -(CH2)3-Brücke gebundenen 3-, 4-, 5-, 6-, 7- oder 8-gliedrigen cycloaliphatischen Rest, der wenigstens einfach mit einer -(C(CH3)2)-oder -(CH2)-Gruppe überbrückt und/oder unsubstituiert oder einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus C1-5-Alkyl, C1-5-Alkoxy, -CF3, CHF2, CH2F und Oxo substituiert sein kann,
oder für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte C1-5-Alkylen-Gruppe gebundenen -C(=O)-OR7-Rest, für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte C1-5-Alkylen-Gruppe gebundenen -O-(C=O)-R8-Rest, oder für einen über eine lineare oder verzweigte, unsubstituierte oder wenigstens einfach substituierte C1-5-Alkylen-Gruppe gebundenen -(C=O)-R9-Rest steht,
besonders bevorzugt für einen linearen oder verzweigten, ggf. eines oder mehrere Sauerstoffatome und/oder eines oder mehrere Schwefelatome als Kettenglied aufweisenden C1-8-Alkyl-Rest, der unsubstituiert oder wenigstens einfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus unsubstituiertem Phenyl, Dimethylamino, Carboxy und -NH-(C=O)-O-C(CH3)3 substituiert sein kann, für einen linearen oder verzweigten, unsubstituierten C2-4-Alkenyl-Rest, für einen Phenyl-Rest, Naphthyl-Rest, Furyl- (Furanyl-)-Rest, Thienyl-(Thiophenyl-)-Rest, [1,2,3]-Triazolyl-Rest, Chromanyl-Rest, Benzo[1.3]dioxolyl-Rest, Benzo[1,2,5]oxadiazolyl-Rest, Pyrimidinyl-Rest, Pyrazolyl-Rest, Pyridinyl-Rest, Isoxazolyl-Rest oder [1,2,3]-Thiadiazolyl-Rest, wobei der zyklische Rest jeweils über eine -(CH2)-, -(CH2)-O-, -CH=CH-, -(CH2)2-, -(CH2)2-O-, oder -(CH2)3-Brücke gebunden sein kann und/oder einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, Methyl, Ethyl, iso-Propyl, n-Propyl, sec-Butyl, tert.-Butyl, n-Butyl, Methoxy, Ethoxy, -CF3,-OCF3, -CH2-O-C(=O)-Phenyl, NO2, -S-CF3, -S-CHF2, -N(CH3)2, -NH-CO-CH3, CN, SO2-NH2, Phenyl und Phenoxy, wobei die letztgenannten Phenyl- und Phenoxy Substituenten selbst einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CH3 und OCH3 substituiert sein können,
für einen ggf. über eine -(CH2)-, -(CH2)2- oder -(CH2)3-Brücke gebundenen Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Imidazolidin, 4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo-[2.2.1]-heptyl-Rest oder Adamantyl-Rest, der unsubstituiert oder einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus C1-5-Alkyl, C1-5-Alkoxy, -CF3, CHF2, CH2F und Oxo substituiert ist,
für einen über eine -(CH2)-, -(CH2)2-, -C(H)(Phenyl)-, oder -C(CH3)2-Gruppe gebundenen -C(=O)-OR7-Rest, für einen über eine -(CH2)-, -(CH2)2-, -C(H)(Phenyl)-, oder -C(CH3)2-Gruppe gebundenen -O-(C=O)-R8-Rest, oder für einen über eine -(CH2)- oder -(CH2)2-Gruppe gebundenen -(C=O)-R9-Rest steht,
ganz besonders bevorzugt für einen linearen oder verzweigten, ggf. eines oder mehrere Sauerstoffatome und/oder eines oder mehrere Schwefelatome als Kettenglied aufweisenden C6-8-Alkyl-Rest, der unsubstituiert oder wenigstens einfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus unsubstituiertem Phenyl, Dimethylamino, Carboxy und -NH-(C=O)-O-C(CH3)3 substituiert sein kann, für einen linearen oder verzweigten, unsubstituierten C2-4-Alkenyl-Rest, für einen Naphthyl-Rest, Furyl- (Furanyl-)-Rest, Thienyl-(Thiophenyl-)-Rest, [1,2,3]-Triazolyl-Rest, Chromanyl-Rest, Benzo[1.3]dioxolyl-Rest, Benzo[1,2,5]oxadiazolyl-Rest, Pyrimidinyl-Rest, Pyrazolyl-Rest, Pyridinyl-Rest, Isoxazolyl-Rest oder [1,2,3]-Thiadiazolyl-Rest, wobei der zyklische Rest jeweils über eine -(CH2)-, -(CH2)-O-, -CH=CH-, -(CH2)2-, -(CH2)2-O-, oder -(CH2)3-Brücke gebunden sein kann und/oder einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, Methyl, Ethyl, iso-Propyl, n-Propyl, sec-Butyl, tert.-Butyl, n-Butyl, Methoxy, Ethoxy, -CF3, -OCF3, -CH2-O-C(=O)-Phenyl, -NO2, -S-CF3, -S-CHF2,-N(CH3)2, -NH-CO-CH3, -CN, -SO2-NH2, Phenyl und Phenoxy, wobei die letztgenannten Phenyl- und Phenoxy Substituenten selbst einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CH3 und OCH3 substituiert sein können,
für 2-Trifluoromethoxy-phenyl, 3- Trifluoromethoxy-phenyl, 4-Trifluoromethoxyphenyl, 2-CF3-S-phenyl, 3-CF3-S-phenyl, 4-CF3-S-phenyl, 2-Cyano-phenyl, 3-Cyanophenyl, 4-Cyano-phenyl, 2-Nitro-phenyl, 3-Nitro-phenyl, 4-Nitro-phenyl, 2-CHF2-S-Phenyl, 3-CHF2-S-Phenyl, 4-CHF2-S-Phenyl, 2-Dimethylamino-phenyl, 3-Dimethylamino-phenyl, 4-Dimethylamino-phenyl, 2-Phenyl-(C=O)-O-CH2-phenyl, 3-Phenyl-(C=O)-O-CH2-phenyl, 4-Phenyl-(C=O)-O-CH2-phenyl, 2-CH3-(C=O)-NH-Phenyl, 3-CH3-(C=O)-NH-Phenyl, 4-CH3-(C=O)-NH-Phenyl, 2-Phenyl-phenyl, 3-Phenyl-phenyl, 4-Phenyl-phenyl, 2-NH2-SO2-Phenyl, 3-NH2-SO2-Pheny, 4-NH2-SO2-Phenyl, Pentafluor-phenyl, 4-Methyl-3-nitro-phenyl, 2-Fluor-benzyl, 3-Fluor-benzyl, 4-Fluor-benzyl, 2-Chlor-benzyl, 3-Chlor-benzyl, 4-Chlor-benzyl, 2-Brom-benzyl, 3-Brom-benzyl, 4-Brom-benzyl, 2-Methyl-benzyl, 3-Methyl-benzyl, 4-Methyl-benzyl, 2-Methoxy-benzyl, 3-Methoxy-benzyl, 4-Methoxy-benzyl, 3,4-Dimethoxy-benzyl, 2,5-Dimethoxy-benzyl, -CH=CH-Phenyl, wobei der Phenyl-Rest in 2-, 3- oder 4- Position einfach oder mehrfach, gleich oder verschieden, mit einem Rest ausgewählt aus der Gruppe bestehend aus F, Cl, Br und CF3 substituiert sein kann, -CH2-O-Phenyl, wobei der Phenyl-Rest in 2-, 3- oder 4- Position einfach oder mehrfach, gleich oder verschieden, mit einem Rest ausgewählt aus der Gruppe bestehend aus F, Cl, Br und CF3 substituiert sein kann
für einen ggf. über eine -(CH2)-, -(CH2)2- oder -(CH2)3-Brücke gebundenen Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl, Imidazolidin, , 4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo-[2.2.1]-heptyl-Rest oder Adamantyl-Rest, der unsubstituiert oder einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus C1-5-Alkyl, C1-5-Alkoxy, -CF3, CHF2, CH2F und Oxo substituiert ist,
für einen über eine -(CH2)-, -(CH2)2-, -C(H)(Phenyl)-, oder -C(CH3)2-Gruppe gebundenen -C(=O)-OR7-Rest, für einen über eine -(CH2)-, -(CH2)2-, -C(H)(Phenyl)-, oder -C(CH3)2-Gruppe gebundenen -O-(C=O)-R8-Rest, oder für einen über eine -(CH2)- oder -(CH2)2-Gruppe gebundenen -(C=O)-R9-Rest steht, und die übrigen Reste R1-R3 und R5 bis R9 die vorstehend genannte Bedeutung haben, jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, oder jeweils in Form entsprechender Solvate.Also preferred are those substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I given above, in which the radical R 4
for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 1-10 alkyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkenyl radical, for a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 2-10 alkynyl radical,
for an unsubstituted or at least monosubstituted 5- to 14-membered aryl or heteroaryl radical which has a linear or branched, unsubstituted or at least monosubstituted, optionally at least one heteroatom as a chain member having C 1-5 alkylene-, C 2-5 alkenylene or C 2-5 alkynylene group bound and / or may be condensed with an unsubstituted or at least monosubstituted monocyclic ring system,
bonded an unsubstituted or at least mono-substituted, optionally one heteroatom having at least as a ring member, optionally via a linear or branched, unsubstituted or at least mono-substituted, optionally at least one heteroatom as chain member C 1-6 alkylene group, C 3 -8 cycloaliphatic radical which may be at least simply bridged with a linear or branched, unsubstituted or at least monosubstituted C 1-6 -alkylene group and / or may be condensed with an unsubstituted or at least monosubstituted monocyclic ring system,
for a C (OO) -OR 7 radical bonded via a linear or branched, unsubstituted or at least monosubstituted C 1-5 -alkylene group, for a C 1 - via a linear or branched, unsubstituted or at least monosubstituted 5 -alkylene group bonded -O- (C = O) -R 8 radical or bonded via a linear or branched, unsubstituted or at least monosubstituted C 1-5 alkylene group - (C = O) -R 9- rest stands,
preferably for a linear or branched, optionally one or more oxygen atoms and / or one or more sulfur atoms as a chain member having C 1-10 alkyl radical which is unsubstituted or at least monosubstituted, identical or different, having a substituent selected from the group may be substituted by phenyl, di- (C 1-5 alkylamino), carboxy and -NH- (C = O) -OC 1-5 alkyl, for a linear or branched, unsubstituted C 2-5 alkenyl radical , a phenyl radical, naphthyl radical, furyl (furanyl) radical, thienyl (thiophenyl) radical or [1,2,3] -triazolyl radical, benzo [1.3] dioxolyl radical, benzo [1,2,5] oxadiazolyl radical, chromanyl radical, pyrimidinyl radical, pyrazolyl radical, pyridinyl radical, isoxazolyl radical or [1,2,3] -thiadiazolyl residue, wherein the cyclic radical in each case via a - (CH 2) -, - (CH 2) - O-, -CH = CH-, - (CH 2) 2 -, - (CH 2 ) 2 -O-, or - (CH 2 ) 3 bridge may be bonded and / or singly or multiply, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I, -CN, -NO 2 , C 1-5 alkyl, C 1-5 alkoxy, C 1-5 perfluoroalkoxy, -C (= O) -C 1-5 alkyl, -C (= O) -OC 1-5 alkyl, - (CH 2 ) 1-3 -OC (= O) -phenyl, -N (CH 3 ) 2 , -S (= O) 2 -C 1-6 -alkyl, -S (= O) 2 -NH 2 , -C (= O) -C 1-5 perfluoroalkyl, -SC 1-5 -alkyl, -S-CH 2 F, -S-CHF 2 , -SCF 3 , -CF 3 , -NH- (C = O) -CH 3 , -SO 2 -NH 2 , -CHF 2 , -CH 2 F, phenyl and phenoxy, the latter phenyl and phenoxy substituents themselves being mono- or polysubstituted by identical or different substituents a substituent selected from the group consisting of F, Cl, Br, -S-CHF 2 , -CF 3 , -CHF 2 , -CH 2 F, CN, NO 2 , C 1-5 -alkyl and C 1-5 - Alkoxy can be substituted,
for a possibly at least one heteroatom as a ring member, optionally via a - (CH 2 ) -, - (CH 2 ) 2 - or - (CH 2 ) 3 bonded 3-, 4-, 5-, 6- , 7 or 8-membered cycloaliphatic radical which bridges at least one simple - (C (CH 3 ) 2 ) or - (CH 2 ) group and / or unsubstituted or mono- or polysubstituted, identical or different, with a substituent selected from the group consisting of C 1-5 alkyl, C 1-5 alkoxy, -CF 3 , CHF 2 , CH 2 F and oxo may be substituted,
or for a via a linear or branched, unsubstituted or at least monosubstituted C 1-5 -Alkylen group bonded -C (= O) -OR 7 radical, for a via a linear or branched, unsubstituted or at least monosubstituted C 1 -5 alkylene group bound -O- (C = O) -R 8 radical, or a via a linear or branched, unsubstituted or at least monosubstituted C 1-5 alkylene group bonded - (C = O) -R 9 -Rest stands,
particularly preferred for a linear or branched, optionally one or more oxygen atoms and / or one or more sulfur atoms as a chain member having C 1-8 alkyl radical which is unsubstituted or at least simply, identically or differently, with a substituent selected from the group consisting of unsubstituted phenyl, dimethylamino, carboxy and -NH- (C = O) -OC (CH 3 ) 3 may be substituted for a linear or branched, unsubstituted C 2-4 alkenyl radical, a phenyl radical, Naphthyl radical, furyl (furanyl) radical, thienyl (thiophenyl) radical, [1,2,3] -triazolyl radical, chromanyl radical, benzo [1,3] dioxolyl radical, benzo [1,2,5] oxadiazolyl radical, pyrimidinyl radical, pyrazolyl radical, pyridinyl radical, isoxazolyl radical Radical or [1,2,3] thiadiazolyl radical, the cyclic radical being in each case via a - (CH 2 ) -, - (CH 2 ) -O-, -CH = CH-, - (CH 2 ) 2 - , - (CH 2 ) 2 -O-, or - (CH 2 ) 3 bridge may be bonded and / or singly or multiply, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I , Methyl, ethyl, isopropyl, n-propyl, sec-butyl, tert-butyl, n-butyl, methoxy, ethoxy, -CF 3 , -OCF 3 , -CH 2 -OC (= O) -phenyl, NO 2 , -S-CF 3 , -S-CHF 2 , -N (CH 3 ) 2 , -NH-CO-CH 3 , CN, SO 2 -NH 2 , phenyl and phenoxy, the latter being phenyl and phenoxy Substituents themselves may be monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, CH 3 and OCH 3 ,
for a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolidine, 4,7,7-trimethyl-3-optionally bonded via a - (CH 2 ) -, - (CH 2 ) 2 - or - (CH 2 ) 3 bridge oxo-2-oxa-bicyclo [2.2.1] heptyl radical or adamantyl radical which is unsubstituted or mono- or polysubstituted, identical or different, with a substituent selected from the group consisting of C 1-5 -alkyl, C Substituted 1-5- alkoxy, -CF 3 , CHF 2 , CH 2 F and oxo,
for a -C (OO) -OR 7 bonded via a - (CH 2 ) -, - (CH 2 ) 2 -, -C (H) (phenyl) -, or -C (CH 3 ) 2 - group Radical, -O- (C = O) attached via a - (CH 2 ) -, - (CH 2 ) 2 -, -C (H) (phenyl) -, or -C (CH 3 ) 2 - group R 8 radical, or represents a - (CH 2 ) - or - (CH 2 ) 2 group bonded - (C = O) -R 9 radical,
very particularly preferably for a linear or branched, optionally one or more oxygen atoms and / or one or more sulfur atoms as a chain member having C 6-8 alkyl radical which is unsubstituted or at least simply, identically or differently, with a substituent selected from A group consisting of unsubstituted phenyl, dimethylamino, carboxy and -NH- (C = O) -OC (CH 3 ) 3 may be substituted, for a linear or branched, unsubstituted C 2-4 alkenyl radical, for a naphthyl radical , Furyl (furanyl) radical, thienyl (thiophenyl) radical, [1,2,3] triazolyl radical, chromanyl radical, benzo [1,3] dioxolyl radical, benzo [1,2,5 ] oxadiazolyl radical, pyrimidinyl radical, pyrazolyl radical, Pyridinyl residue, isoxazolyl residue, or [1,2,3] -thiadiazolyl residue, wherein the cyclic radical in each case via a - (CH 2) -, - (CH 2) - O-, -CH = CH-, - (CH 2 ) 2 -, - (CH 2 ) 2 -O-, or - (CH 2 ) 3 may be bonded and / or single or multiple, identical or different, having a substituent selected from the group consisting of F , Cl, Br, I, methyl, ethyl, iso-propyl, n-propyl, sec-butyl, tert-butyl, n-butyl, methoxy, ethoxy, -CF 3 , -OCF 3 , -CH 2 -OC ( = O) -phenyl, -NO 2 , -S-CF 3 , -S-CHF 2 , -N (CH 3 ) 2 , -NH-CO-CH 3 , -CN, -SO 2 -NH 2 , phenyl and Phenoxy, where the last-mentioned phenyl and phenoxy substituents themselves may be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, CH 3 and OCH 3 ,
for 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-CF 3 -S-phenyl, 3-CF 3 -S-phenyl, 4-CF 3 -S-phenyl, 2-cyano-phenyl, 3-cyanophenyl, 4-cyano-phenyl, 2-nitro-phenyl, 3-nitro-phenyl, 4-nitro-phenyl, 2-CHF 2 -S-phenyl, 3-CHF 2 -S-phenyl, 4-CHF 2 -S-phenyl, 2-dimethylamino-phenyl, 3-dimethylamino-phenyl, 4-dimethylamino-phenyl, 2-phenyl- (C = O) -O-CH 2 -phenyl, 3-phenyl- (C = O) - O-CH 2 -phenyl, 4-phenyl- (C = O) -O-CH 2 -phenyl, 2-CH 3 - (C = O) -NH-phenyl, 3-CH 3 - (C = O) - NH-phenyl, 4-CH 3 - (C =O) -NH-phenyl, 2-phenyl-phenyl, 3-phenyl-phenyl, 4-phenyl-phenyl, 2-NH 2 -SO 2 -phenyl, 3-NH 2 -SO 2 -pheny, 4-NH 2 -SO 2 -phenyl, pentafluorophenyl, 4-methyl-3-nitrophenyl, 2- fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2 Chloro-benzyl, 3-chloro-benzyl, 4-chloro-benzyl, 2-bromo-benzyl, 3-bromo-benzyl, 4-bromo-benzyl, 2-methyl-benzyl, 3-methyl-benzyl, 4-methyl benzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, -CH = CH-phenyl, w ei the phenyl radical in the 2-, 3- or 4- position may be monosubstituted or polysubstituted, identically or differently, with a radical selected from the group consisting of F, Cl, Br and CF 3 , -CH 2 -O- Phenyl, wherein the phenyl radical in the 2-, 3- or 4- position may be mono- or polysubstituted, identically or differently, with a radical selected from the group consisting of F, Cl, Br and CF 3
for a possibly via a - (CH 2 ) -, - (CH 2 ) 2 - or - (CH 2 ) 3 bonded cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolidine,, 4,7,7-trimethyl-3 -oxo-2-oxa-bicyclo [2.2.1] heptyl radical or adamantyl radical which is unsubstituted or mono- or polysubstituted by identical or different substituents is substituted from the group consisting of C 1-5 -alkyl, C 1-5 -alkoxy, -CF 3 , CHF 2 , CH 2 F and oxo,
for a -C (OO) -OR 7 bonded via a - (CH 2 ) -, - (CH 2 ) 2 -, -C (H) (phenyl) -, or -C (CH 3 ) 2 - group Radical, -O- (C = O) attached via a - (CH 2 ) -, - (CH 2 ) 2 -, -C (H) (phenyl) -, or -C (CH 3 ) 2 - group R 8 radical, or represents a - (CH 2 ) - or - (CH 2 ) 2 group bonded - (C = O) -R 9 radical, and the remaining radicals R 1 -R 3 and R 5 to R 9 have the abovementioned meaning, in each case optionally in the form of one of their pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Ebenfalls bevorzugt sind substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I, in denen die Reste R5 und R6, jeweils unabhängig voneinander, für einen linearen oder verzweigten C1-5-Alkyl-Rest, einen linearen oder verzweigten C2-5-Alkenyl-Rest oder für einen linearen oder verzweigten C2-5-Alkinyl-Rest, vorzugsweise für einen Methyl-, Ethyl-, n-Propyl oder iso-Propyl-Rest stehen, und die jeweils die übrigen Reste R1-R4 und R7-R9 die vorstehend genannte Bedeutung haben, jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, oder jeweils in Form entsprechender Solvate.Also preferred are substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I given above, in which the radicals R 5 and R 6 , in each case independently of one another, represent a linear or branched C 1 5- alkyl radical, a linear or branched C 2-5 alkenyl radical or a linear or branched C 2-5 alkynyl radical, preferably a methyl, ethyl, n-propyl or iso-propyl Rest are, and in each case the remaining radicals R 1 -R 4 and R 7 -R 9 have the abovementioned meaning, in each case optionally in the form of one of their pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers , in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.

Bevorzugt sind auch substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I, worin die Reste R7 und R8, jeweils unabhängig voneinander, für einen Wasserstoff-Rest, für einen linearen oder verzweigten C1-5-Alkyl-Rest, einen linearen oder verzweigten C2-5-Alkenyl-Rest, einen linearen oder verzweigten C2-5-Alkinyl-Rest, oder für einen ggf. wenigstens einfach substituierten Phenyl- oder Naphthyl-Rest stehen, vorzugsweise für einen Methyl-, Ethyl-, n-Propyl, iso-Propyl-Rest oder unsubstituierten Phenyl-Rest stehen, und jeweils die übrigen Reste R1-R6 und R9 die vorstehend genannte Bedeutung haben, jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, oder jeweils in Form entsprechender Solvate.Also preferred are substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I given above, wherein the radicals R 7 and R 8 , each independently of one another, are a hydrogen radical, a linear or branched C 1-5 -alkyl radical, a linear or branched C 2-5 -alkenyl radical, a linear or branched C 2-5 -alkynyl radical, or, if appropriate, at least simply are substituted phenyl or naphthyl radical, are preferably a methyl, ethyl, n-propyl, iso-propyl radical or unsubstituted phenyl radical, and in each case the other radicals R 1 -R 6 and R 9 are those mentioned above Have meaning, in each case optionally in the form of one of their pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of appropriate salts, or in each case in the form of corresponding solvates.

Bevorzugt sind weiterhin substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I, worin der Rest R9 für einen linearen oder verzweigten C1-5-Alkyl-Rest, einen linearen oder verzweigten C2-5-Alkenyl-Rest, einen linearen oder verzweigten C2-5-Alkinyl-Rest, vorzugsweise für einen Methyl-, Ethyl-, n-Propyl oder iso-Propyl-Rest steht, und jeweils die übrigen Reste R1-R8 die vorstehend genannte Bedeutung haben, jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, oder jeweils in Form entsprechender Solvate.Preference is furthermore given to substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the abovementioned general formula I in which the radical R 9 is a linear or branched C 1-5 -alkyl radical, a linear or branched chain radical branched C 2-5 alkenyl radical, a linear or branched C 2-5 alkynyl radical, preferably represents a methyl, ethyl, n-propyl or iso-propyl radical, and in each case the other radicals R 1 R 8 have the abovementioned meaning, in each case optionally in the form of one of their pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case Form of corresponding salts, or in each case in the form of corresponding solvates.

Besonders bevorzugt sind substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I

Figure imgb0002
worin
R1 für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten C1-4-Alkyl-Rest, für einen linearen oder verzweigten, unsubstituierten C2-5-Alkenyl-Rest, für einen linearen oder verzweigten, unsubstituierten C2-3-Alkinyl-Rest, für einen Phenyl- oder Naphthyl-Rest, der unsubstituiert oder einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, -CN, -NO2, C1-5-Alkyl, C1-5-Alkoxy, -C(=O)-C1-5-Alkyl, -C(=O)-O-C1-5-Alkyl, -S(=O)2-C1-6-alkyl, -C(=O)-C1-5-Perfluoroalkyl, -CF3, -CHF2 und -CH2F substituiert und/oder über eine -(CH2)-, - (CH2)2-, -(CH2)3- oder -(CH2)2-O-Brücke gebunden ist, für einen über eine -(CH2)-Gruppe gebundenen -C(=O)-OR5-Rest oder für einen über eine -(CH2)-, -(CH2)2-, - (CH2)3- oder -(CH2)4-Gruppe gebundenen -O-C(=O)-R6-Rest steht,
R2 für einen Wasserstoff-Rest, für einen linearen oder verzweigten, unsubstituierten, ggf. eines oder mehrere Schwefelatome als Kettenglied aufweisenden C1-5-Alkyl-Rest oder für einen Phenyl-Rest steht, wobei der Phenyl-Rest einfach oder mehrfach, gleich oder verschieden, mit einem Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, -CN, -NO2, C1-5-Alkyl, C1-5-Alkoxy, -C(=O)-C1-5-Alkyl, -C(=O)-O-C1-5-Alkyl, -S(=O)2-C1-6-alkyl, -C(=O)- C1-5-Perfluoroalkyl, -CF3, CHF2 und CH2F substituiert und/oder über eine -(CH2)-Brücke gebunden sein kann,
R3 für einen Wasserstoff-Rest, für einen Biphenyl-Rest, der über eine -(CH2)-, - (CH2)2- oder -(CH2)3-Brücke gebunden ist, oder für eine C(=O)-R4-Gruppe steht,
R4 für einen Rest steht, der ausgewählt ist aus der Gruppe bestehend aus Methyl, Ethyl, iso-Propyl, n-Propyl, sec-Butyl, Isobutyl, tert-Butyl, n-Butyl, n-Pentyl, 1-Methylbutyl, 2-Dimethyl-propyl, 1-Ethyl-propyl, 1-Propyl-butyl, 1-Ethyl-pentyl, Dimethylaminomethyl, -CH2-CH2-CH=CH2, -CH2-O-CH3, -CH2-O-CH2-CH2-O-CH3, - CH2-CH2-Phenyl, -CH2-O-Phenyl, -CH2-O-CH2-Phenyl, -CH2-CH2-CH2-O-Phenyl, - C(H)(Phenyl)(C2H5), -C(H)(CH3)-O-Phenyl, -CH2-CH2-(C=O)-CH3, -CH2-O-(C=O)-CH3, -CH2-CH2-(C=O)-O-C2H5, -CH2-O-(C=O)-Phenyl, -CH2-(C=O)-O-CH2-CH3, -C(H)(Phenyl)-(C=O)-CH3, -C(H)(Phenyl)-O-(C=O)-CH3, - C(CH3)2-O-(C=O)-CH3, -C(H)(NH-(C=O)-O-(CH3)3)(CH2-O-CH2-Phenyl), -C(CH3)2-CH2-COOH, unsubstituiertem Phenyl, 2-Fluor-phenyl-, 3-Fluor-phenyl-, 4-Fluor-phenyl-, 2-Chlor-phenyl-, 3-Chlor-phenyl-, 4-Chlor-phenyl-, 2-Brom-phenyl, 3-Brom-phenyl, 4-Brom-phenyl, 2-Iod-phenyl, 3-Iod-phenyl, 4-Iod-phenyl, 2-Methyl-phenyl, 3-Methyl-phenyl, 4-Methyl-phenyl, 2-Ethyl-phenyl, 3-Ethyl-phenyl, 4-Ethyl-phenyl, 2-n-Propyl-phenyl, 3-n-Proyl-phenyl, 4-n-Propyl-phenyl, 2-tert.-Butyl-phenyl, 3-tert.-Butylphenyl, 4-tert.-Butyl-phenyl, 2-Methoxy-phenyl, 3-Methoxy-phenyl, 4-Methoxy-phenyl, 2-Ethoxy-phenyl, 3-Ethoxy-phenyl, 4-Ethoxy-phenyl, 2-Trifluoromethyl-phenyl, 3-Trifluoromethyl-phenyl, 4-Trifluoromethyl-phenyl, 2-Trifluoromethoxy-phenyl, 3-Trifluoromethoxy-phenyl, 4-Trifluoromethoxy-phenyl, 2-CF3-S-phenyl, 3-CF3-S-phenyl, 4-CF3-S-phenyl, 2-Cyano-phenyl, 3-Cyano-phenyl, 4-Cyano-phenyl, 2-Nitrophenyl, 3-Nitro-phenyl, 4-Nitro-phenyl, 2-CHF2-S-Phenyl, 3-CHF2-S-Phenyl, 4-CHF2-S-Phenyl, 2-Dimethylamino-phenyl, 3-Dimethylamino-phenyl, 4-Dimethylaminophenyl, 2-Phenyl-(C=O)-O-CH2-phenyl, 3-Phenyl-(C=O)-O-CH2-phenyl, 4-Phenyl-(C=O)-O-CH2-phenyl, 2-CH3-(C=O)-NH-Phenyl, 3-CH3-(C=O)-NH-Phenyl, 4-CH3-(C=O)-NH-Phenyl, 2-Phenyl-phenyl, 3-Phenyl-phenyl, 4-Phenyl-phenyl, 2-NH2-SO2-Phenyl, 3-NH2-SO2-Pheny, 4-NH2-SO2-Phenyl, 2,4-Dimethoxy-phenyl, 2,5-Dimethoxy-phenyl, 3,5-Dimethoxy-phenyl, 3,4-Dimethoxy-phenyl, 2,3-Dimethyl-phenyl, 2,3-Dichlorphenyl, 3,4-Dichlorphenyl, 2,6-Dichlorphenyl, 2,3-Difluorphenyl, 3,4-Difluorphenyl, 3,5-Difluor-phenyl, Pentafluor-phenyl, 2-Chlor-6-Fluor-phenyl, 4-Brom-3-methyl-phenyl, 3-Fluor-4-methyl-phenyl, 3-Chlor-2-Fluor-phenyl, 2-Chlor-4-nitro-phenyl, 5-Fluor-2-trifluoromethyl-phenyl, 3-Fluor-4-trifluoromethyl, 4-Methyl-3-nitro-phenyl, 2-Chlor-5-trifluoro-methyl, 2,5-Bis-trifluoromethyl-phenyl, 3,5-Bis-trifluoromethyl-phenyl, 2-Chlor-6-fluor-3-methyl-phenyl, 6-Chlor-2-fluor-3-methylphenyl, 2,6-Difluor-4-methyl-phenyl, 2,6-Difluor-3-methyl-phenyl, 3,4,5-Trimethoxy-phenyl, 2,3-Difluor-4-methyl-phenyl, 2-Fluor-benzyl, 3-Fluor-benzyl, 4-Fluor-benzyl, 2-Chlor-benzyl, 3-Chlor-benzyl, 4-Chlor-benzyl, 2-Brom-benzyl, 3-Brom-benzyl, 4-Brom-benzyl, 2-Methyl-benzyl, 3-Methyl-benzyl, 4-Methyl-benzyl, 2-Methoxy-benzyl, 3-Methoxy-benzyl, 4-Methoxy-benzyl, 3,4-Dimethoxy-benzyl, 2,5-Dimethoxy-benzyl, - CH=CH-Phenyl, wobei der Phenyl-Rest in 2-, 3- oder 4- Position einfach oder mehrfach, gleich oder verschieden, mit einem Rest ausgewählt aus der Gruppe bestehend aus F, Cl, Br und CF3 substituiert sein kann, -CH2-O-Phenyl, wobei der Phenyl-Rest in 2-, 3- oder 4- Position einfach oder mehrfach, gleich oder verschieden, mit einem Rest ausgewählt aus der Gruppe bestehend aus F, Cl, Br und CF3 substituiert sein kann, 1-Naphthyl, 2-Naphthyl, 2-Thienyl, 3-Thienyl, 3-Chlorthien-2-yl, 2-Furanyl, 3-Furanyl, 2,5-Dimethyl-Furan-3-yl, 5-tert.-Butyl-2-methyl-furan-3-yl, Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, 2-Chlor-pyridin-4-yl , 6-Chlor-pyridin-3-yl, 2-Chlor-pyridin-3-yl, 2-Ethylsulfanyl-pyridin-3-yl, 2-Phenoxy-pyridin-3-yl, 2-Methylsulfanyl-pyridin-3-yl, 2-Methyl-6-trifluoromethyl-pyridin-3-yl, Isoxazol-5-yl, 5-Methyl-isoxazol-3-yl, 3-(2-Chlor-6-Fluor-phenyl)-5-methyl-isoxazol-4-yl, 3-(2-Chlor-phenyl)-5-methyl-isoxazol-4-yl, 3-(2,6-Dichlor-phenyl)-5-methyl-isoxazol-4-yl, 5-tert.-Butyl-2-methyl-2H-pyrazol-3-yl, 1-Phenyl-5-n-Propyl-1H-pyrazol-4-yl, 1-(4-Chlor-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl, 2-tert-Butyl-5-methyl-2H-pyrazol-3-yl, 5-Methyl-2-Phenyl-2H-[1,2,3]triazol-4-yl, 4-Methyl-[1,2,3]thiadiazol-5-yl, 2-Chlor-4-trifluormethyl-pyrimidin-5-yl, 2-Chlor-4-trifluoromethyl-pyrimidin-5-yl, Benzo[1,2,5]oxadiazol-5-yl, Benzo[1.3]dioxol-5-yl, 6-Chlor-2H-chroman-3-yl, Imidazolidin-2,4-dion-5-yl-methyl, Cyclopropyl, Cyclobutyl, ggf. über eine -(CH2)- oder -(CH2)2-Brücke gebundenem Cyclopentyl, Cyclohexyl, 4,7,7-Trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptyl und Adamantyl.
Vorzugsweise sind Verbindungen der vorstehend angegebenen Formel I, in denen

  • A)
    R1 für einen Wasserstoff-Rest, einen C1-6-Alkyl-Rest, einen C1-6-Alkoxy-Rest, einen C2-6-Hydroxyalkyl-Rest, einen C2-6Alkenyl-Rest, einen C2-6-Alkinyl-Rest, einen Phenyl-Rest oder für einen einfach, zweifach oder dreifach mit einem Phenyl-Rest substituierten C1-6-Alkyl-Rest steht,
    R2 für einen Wasserstoff-Rest, einen C1-6-Alkyl-Rest, einen C1-6-Alkoxy-Rest, einen C2-6-Hydroxyalkyl-Rest, einen C2-5Alkenyl-Rest, einen C2-6-Alkinyl-Rest, einen Phenyl-Rest, einen einfach, zweifach oder dreifach mit einem Phenyl-Rest substituierten C1-6-Alkyl-Rest, eine -O-C1-6-Alkanoyl-Rest, einen OH-Rest, einen -0-C1-6-Alkyl-Rest, einen -O-C1-6-Alkoxy-Rest, einen -O-C2-6-Hydroxyalkyl-Rest, einen - O-C2-6Alkenyl-Rest, einen -O-C2-6-Alkinyl-Rest, einen -O-Phenyl-Rest oder für einen einfach, zweifach oder dreifach mit einem Phenyl-Rest substituierten -O-C1-6-Alkyl-Rest,
    R3 für einen Wasserstoff-Rest, einen C1-6-Alkyl-Rest, einen C2-6-Alkenyl-Rest, einen C2-6-Alkinyl-Rest, einen C3-7-Cycloalkyl-Rest, einen mit 1-6 Halogenatomen substituierten C1-6-Alkyl-Rest, einen Hydroxy-C1-6-Alkyl-Rest, einen C1-6-Alkoxy-Rest, einen C1-6-Alkylthio-Rest, einen C1-6-Alkoxy-C1-6-Alkyl-Rest, einen Carboxy-C1-6-Alkyl-Rest, einen (C1-6-Alkoxy)carbonyl-C1-6-Alkyl-Rest, einen Amino-C1-6-alkyl-Rest, einen mono-(C1-6-Alkyl)-amino-Rest, einen di-(C1-6-Alkyl)-amino-Rest, einen 2-oxopyrrolidin-1-yl-methyl-Rest, einen Aryl-Rest, einen Diarylmethylol-Rest, einen mit ein oder zwei Aryl-Resten substituierter C1-6-Alkyl-Rest, einen C1-6-Alkanoyl-Rest oder einen Arylcarbonyl-Rest steht, wobei Aryl jeweils für einen unsubstituierten Phenyl-Rest oder für einen Phenyl-Rest steht, der mit 1-3-Substituenten ausgewählt aus der Gruppe bestehend aus Halogen, C1-6-Alkyl, C1-6-Alkoxy und CF3 substituiert ist, sowie deren physiologische verträgliche Salze, Enantiomeren und Racemate,
    und/oder
  • B)
    die Reste R1, R2 und R3 jeweils für einen Wasserstoff-Rest oder einen Kohlenwasserstoff-Rest stehen sowie jeweils deren Salzen
    ausgenommen.
    Ganz besonders bevorzugt sind substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I ausgewählt aus der Gruppe bestehend aus
    (1)
    3-(S)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (2)
    8-(2,4-Dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (3)
    3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (4)
    8-Acetyl-3-(S)-benzyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (5)
    3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (6)
    3-(S)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (7)
    8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (8)
    1,3-(S)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (9)
    8-Acetyl-1,3-(S)-dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (10)
    3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-methoxy-benzyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (11)
    3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-fluor-benzyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (12)
    1,3-(S,R)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2on,
    (13)
    3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-methoxy-benzyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (14)
    3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-fluor-benzyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (15)
    1,3-(S,R)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (16)
    1-Benzyl-8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (17)
    1,3-(S)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (18)
    1,3-(S)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (19)
    8-Acetyl-1,3-(S)-dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (20)
    3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-methoxy-benzyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (21)
    3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-fluor-benzyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (22)
    1,3-(S,R)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (23)
    3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-methoxy-benzyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (24)
    3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-fluor-benzyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (25)
    1,3-(S,R)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (26)
    1-Benzyl-8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (27)
    1,3-(S)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (28)
    1-Benzyl-8-(2,4-dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (29)
    1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (30)
    1-Benzyl-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (31)
    1,3-(S)-Dibenzyl-8-butyryl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (32)
    1,3(S)-Dibenzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (33)
    1,3-(S)-Dibenzyl-8-(2,3-difluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (34)
    1,3-(S)-Dibenzyl-8-[2-(4-chlor-phenoxy)-acetyl]-1,4,8-triazaspiro[4.5]decan-2-on,
    (35)
    1,3-(S)-Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (36)
    1,3-(S)-Dibenzyl-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (37)
    1,3-(S)-Dibenzyl-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (38)
    1,3-(S)-Dibenzyl-8-(naphthalin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (39)
    1,3-(S)-Dibenzyl-8-(furan-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (40)
    1,3-(S)-Dibenzyl-8-(3-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (41)
    1,3-(S)-Dibenzyl-8-(4-fluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (42)
    1-Benzyl-8-(4-fluor-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (43)
    1,3-(S)-Dibenzyl-8-butyryl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (44)
    1,3-(S)-Dibenzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (45)
    1,3-(S)-Dibenzyl-8-(2,3-difluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (46)
    1,3-(S)-Dibenzyl-8-[2-(4-chlor-phenoxy)-acetyl]-1,4,8-triazaspiro[4.5]decan-2-on,
    (47)
    1,3-(S)-Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (48)
    1,3-(S)-Dibenzyl-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (49)
    1,3-(S)-Dibenzyl-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (50)
    1,3-(S)-Dibenzyl-8-(naphthalin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (51)
    1,3-(S)-Dibenzyl-8-(furan-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (52)
    1,3-(S)-Dibenzyl-8-(3-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (53)
    1,3-(S)-Dibenzyl-8-(4-fluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (54)
    1-Benzyl-8-(4-fluor-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (55)
    N-[4-(3-Isobutyl-2-oxo-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-8-carbonyl)-phenyl]-acetamid,
    (56)
    1-(2-Phenoxy-ethyl)-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (57)
    2-(2-Oxo-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzonitril,
    (58)
    8-(2,4-Dimethoxy-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (59)
    2-[8-(2-Ethyl-butyryl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (60)
    4-(2-Isobutyl-3-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl)-benzonitril,
    (61)
    8-(6-Chlor-pyridin-3-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (62)
    2-[8-(2-Methyl-pentanoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (63)
    1-Benzyl-8-(biphenyl-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (64)
    3-Isobutyl-8-(5-methyl-isoxazol-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (65)
    3-Oxo-3-[2-oxo-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]dec-8-yl]-propionsäureethylester,
    (66)
    8-(2-Chlor-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (67)
    8-Cyclopentancarbonyl-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (68)
    8-(Furan-2-carbonyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (69)
    3-Benzyl-8-(2-ethylsulfanyl-pyridin-3-carbonyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (70)
    3-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (71)
    8-(2-Benzyloxy-acetyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (72)
    3-Benzyl-8-(2-methoxy-acetyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (73)
    8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (74)
    2-{8-[3-(2-chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl}-benzonitril,
    (75)
    3-Benzyl-8-(2-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (76)
    3-Benzyl-8-(3-dimethylamino-benzoyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (77)
    8-(3-Methyl-benzoyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (78)
    3-Isopropyl-1-(3-methyl-but-2-enyl)-8-(pyridin-4-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (79)
    1-Benzyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (80)
    2-{8-[3-(2-chlor-phenyl)-acryloyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl}-benzonitril,
    (81)
    8-(3-Chlor-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (82)
    Essigsäure 2-(2-benzyl-3-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl)-2-oxo-1-phenyl-ethylester,
    (83)
    8-(3,5-Dimethoxy-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (84)
    3-Benzyl-8-(isoxazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (85)
    8-(3-Chlor-thiophen-2-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (86)
    3-Isopropyl-8-pentafluorbenzoyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (87)
    8-(2,5-Dimethyl-furan-3-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (88)
    1-Butyl-8-[2-(3,4-dimethoxy-phenyl)-acetyl]-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (89)
    1-Benzyl-3-isopropyl-8-(pyridin-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (90)
    1,3-Dibenzyl-8-(3-dimethylamino-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (91)
    5-{2-[1-(4-Fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-ethyl}-imidazolidin-2,4-dion,
    (92)
    8-(Biphenyl-4-carbonyl)-1-(4-fluor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (93)
    2-[2-Oxo-8-(2-propyl-pentanoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (94)
    2-[8-(Furan-2-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (95)
    8-[2-(4-Chlor-phenoxy)-acetyl]-3-isobutyl-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (96)
    1,3-Dibenzyl-8-(4-brom-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (97)
    8-(3-Difluormethylsulfanyl-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (98)
    8-(2,3-Dimethyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (99)
    3-Benzyl-8-(2,3-dimethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (100)
    1-(4-Fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-8-(pyridin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (101)
    3-Benzyl-8-(3,3-dimethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (102)
    2-[8-(3-Dimethylamino-benzoyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (103)
    3-[8-(2-Methoxy-acetyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (104)
    Essigsäure 2-(3-benzyl-1-methyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl)-2-oxo-1-phenyl-ethylester,
    (105)
    2-[8-[2-(2-Methoxy-ethoxy)-acetyl]-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (106)
    3-Benzyl-8-[3-(2-chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-1,4,8-triaza-spiro[4.5]decan-2-on,
    (107)
    8-(2-Chlor-6-fluor-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (108)
    1-Methyl-3-(2-methylsulfanyl-ethyl)-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (109)
    8-(2-Chlor-pyridin-3-carbonyl)-1-(4-fluor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (110)
    8-(2-Ethyl-butyryl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (111)
    1-Methyl-3-(2-methylsulfanyl-ethyl)-8-(2-phenoxy-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (112)
    8-(3-Fluor-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (113)
    3-Benzyl-8-(naphthalin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (114)
    8-Cyclohexancarbonyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (115)
    8-(2-Phenoxy-acetyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (116)
    4-[1-Butyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzonitril,
    (117)
    3-Benzyl-8-(3,3-dimethyl-butyryl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (118)
    3-Benzyl-8-(4-propyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (119)
    3-Isopropyl-8-(2-phenoxy-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (120)
    1-Butyl-8-hexanoyl-3-Isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (121)
    8-(4-Brom-3-methyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (122)
    8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (123)
    1-(2-Fluor-benzyl)-3-isobutyl-8-(3-methyl-benzoyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (124)
    8-(2-Ethyl-hexanoyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (125)
    3-Benzyl-8-(3,4-difluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (126)
    3-Benzyl-8-(4-ethoxy-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (127)
    1-Benzyl-8-(6-chlor-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (128)
    8-(3-Dimethylamino-benzoyl)-1-(3,5-dimethyl-benzyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (129)
    3-[8-(Benzo[1,3]dioxol-5-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (130)
    3-Benzyl-1-methyl-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (131)
    8-(4-Ethoxy-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (132)
    3-Benzyl-8-(2-benzyloxy-acetyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan2-on,
    (133)
    8-(3,4-Difluor-benzoyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (134)
    3-Benzyl-1-methyl-8-(2-methylsulfanyl-pyridin-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (135)
    1-Butyl-8-(4-methoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (136)
    1,3-Dibenzyl-8-(2-ethylsulfanyl-pyridin-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (137)
    3-Benzyl-8-(3-difluormethylsulfanyl-benzoyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (138)
    1-(4-Fluor-benzyl)-8-(furan-2-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (139)
    3-Benzyl-8-(3-fluor-4-methyl-benzoyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (140)
    8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (141)
    1-Butyl-8-(6-Chlor-2H-chroman-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (142)
    3-[8-(3-Methoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitril,
    (143)
    8-Cyclobutancarbonyl-3-(2-methylsulfanyl-ethyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (144)
    3-Benzyl-1-butyl-8-(furan-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (145)
    1-Benzyl-8-(3-chlor-thiophen-2-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (146)
    3-Benzyl-8-(2,5-bis-trifluormethyl-benzoyl)-1-butyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (147)
    8-(3-Chlor-2-fluor-benzoyl)-1-(3,5-dimethyl-benzyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (148)
    1-Benzyl-8-(2-chlor-pyridin-3-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (149)
    3-Isobutyl-8-pentafluorbenzoyl-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (150)
    8-(2-Benzyloxy-acetyl)-1-butyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (151)
    8-(Furan-2-carbonyl)-3-isobutyl-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (152)
    1-Butyl-3-(2-methylsulfanyl-ethyl)-8-(4-phenoxy-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (153)
    3-Benzyl-8-(6-chlor-pyridin-3-carbonyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (154)
    1-(2-Fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-8-(2-phenoxy-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (155)
    1-(2-Fluor-benzyl)-3-isobutyl-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (156)
    8-[2-(3-Chlor-phenoxy)-acetyl]-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (157)
    8-(2,3-Dimethyl-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (158)
    3-Isopropyl-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (159)
    3-Benzyl-1-methyl-8-(5-methyl-2-phenyl-2H-[1,2,3]triazole-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (160)
    8-[3-(2-Chlor-phenyl)-5-methyl-isoxazol-4-carbonyl]-1-(3,5-dimethyl-benzyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (161)
    1-(2-Fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-8-(pyridin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (162)
    1-Benzyl-3-(2-methylsulfanyl-ethyl)-8-(2-phenoxy-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (163)
    1,3-Dibenzyl-8-(3-chlor-thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (164)
    3-Benzyl-8-(4-tert-butyl-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (165)
    2-[3-Isobutyl-8-(2-methoxy-acetyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (166)
    3-Benzyl-1-butyl-8-(5-fluor-2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (167)
    3-Benzyl-8-[2-(4-methoxy-phenyl)-acetyl]-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (168)
    1,3-Dibenzyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (169)
    1-Benzyl-3-isopropyl-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (170)
    1-Benzyl-8-(4-ethoxy-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (171)
    3-Benzyl-1-butyl-8-cyclohexancarbonyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (172)
    3-[8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (173)
    1-(2-Fluor-benzyl)-3-isobutyl-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (174)
    1-Methyl-3-(2-methylsulfanyl-ethyl)-8-(2-propyl-pentanoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (175)
    3-Benzyl-1-methyl-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (176)
    3-Isobutyl-1-prop-2-ynyl-8-(3-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (177)
    3-Benzyl-8-(furan-2-carbonyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (178)
    1-Methyl-3-(2-methylsulfanyl-ethyl)-8-(naphthalin-1-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (179)
    3-Benzyl-1-butyl-8-(3-cyclopentyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (180)
    1-(3,5-Dimethyl-benzyl)-3-(2-methylsulfanyl-ethyl)-8-pentanoyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (181)
    3-Benzyl-1-butyl-8-(2-methoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (182)
    3-Benzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (183)
    1-Benzyl-8-(3-difluormethylsulfanyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (184)
    8-(2-Chlor-6-fiuor-3-methyl-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (185)
    4-[3-Isopropyl-8-(2-methylsulfanyl-pyridin-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (186)
    8-[2-(2,5-Dimethoxy-phenyl)-acetyl]-1-(2-fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (187)
    8-(5-tert-Butyl-2-methyl-furan-3-carbonyl)-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (188)
    8-(2-Cyclopentyl-acetyl)-1-(4-fluor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (189)
    4-[8-(3,3-Dimethyl-butyryl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (190)
    3-[8-Cyclopropancarbonyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (191)
    3-[3-(2-Methylsulfanyl-ethyl)-2-oxo-8-(3-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (192)
    1-Butyl-8-(2-cyclopentyl-acetyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (193)
    3-Benzyl-1-butyl-8-(pyridin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (194)
    3-Benzyl-8-[3-(2-chlor-phenyl)-acryloyl]-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (195)
    4-[8-(3-fluor-4-trifluormethyl-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (196)
    8-[3-(2,6-Dichlor-phenyl)-5-methyl-isoxazol-4-carbonyl]-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (197)
    1-Butyl-8-cyclohexancarbonyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (198)
    3-Benzyl-1-butyl-8-(4-iod-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on
    (199)
    1-Methyl-3-(2-methylsulfanyl-ethyl)-8-[3-(3-trifluormethyl-phenyl)-acryloyl]-1,4,8-triaza-spiro[4.5]decan-2-on,
    (200)
    1,3-Dibenzyl-8-(4-phenoxy-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on
    (201)
    3-Benzyl-8-(2-chlor-6-fluor-benzoyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (202)
    4-[8-(2-Chlor-pyridin-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (203)
    8-(2,5-Dimethyl-furan-3-carbonyl)-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (204)
    8-(Biphenyl-4-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (205)
    8-(3-Chlor-thiophen-2-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (206)
    1-(4-Fluor-benzyl)-8-[2-(4-methoxy-phenyl)-acetyl]-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (207)
    1-Benzyl-3-isopropyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (208)
    2-[3-Isopropyl-8-(2-methylsulfanyl-pyridin-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (209)
    3-[8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (210)
    1-Butyl-8-(2,5-dimethyl-furan-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (211)
    8-(3-Cyclopentyl-propionyl)-1-(2-fluor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (212)
    1-Benzyl-8-(3-cyclopentyl-propionyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (213)
    3-(2-Methylsulfanyl-ethyl)-8-(4-phenoxy-butyryl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (214)
    1,3-Dibenzyl-8-(3-phenyl-acryloyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (215)
    3-Benzyl-8-(6-chlor-2-fluor-3-methyl-benzoyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (216)
    8-[3-(2-Chlor-phenyl)-acryloyl]-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (217)
    2-[3-Isopropyl-2-oxo-8-(3-phenyl-acryloyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (218)
    3-Benzyl-1-methyl-8-(4-methyl-3-nitro-benzoyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (219)
    1-Benzyl-8-(furan-2-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (220)
    1-Butyl-8-(3,5-dimethoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (221)
    1,3-Dibenzyl-8-(3,3-dimethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (222)
    8-(2,6-Difluor-3-methyl-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (223)
    2-[8-(2-Chlor-6-fluor-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (224)
    8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-3-isopropyl-1-(3-methyl-but-2-enyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (225)
    3-Isobutyl-1-prop-2-ynyl-8-(4-trifluormethoxy-benzoyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (226)
    1-Benzyl-8-(2-chlor-6-fluor-3-methyl-benzoyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (227)
    Benzoesäure 2-(1-benzyl-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl)-benzylester,
    (228)
    1,3-Dibenzyl-8-(2-phenyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (229)
    3-Benzyl-1-methyl-8-(4-nitro-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (230)
    3-Benzyl-1-methyl-8-(5-methyl-isoxazol-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (231)
    1-Benzyl-8-(6-chlor-2-fluor-3-methyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (232)
    1-Benzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-on,
    (233)
    3-Benzyl-8-(6-chlor-2H-chroman-3-carbonyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (234)
    3-Benzyl-1-butyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (235)
    3-Benzyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (236)
    2-[8-(6-Chlor-2H-chroman-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (237)
    2-[8-(5-Methyl-isoxazol-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (238)
    2-[8-(3-Chlor-2-fluor-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (239)
    4-[8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (240)
    3-Benzyl-1-butyl-8-(5-tert-butyl-2-methyl-2H-pyrazol-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (241)
    3-Benzyl-1-butyl-8-(2-chlor-4-trifluormethyl-pyrimidin-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (242)
    3-Benzyl-8-(5-methyl-isoxazol-3-carbonyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (243)
    4-[8-(2-Chlor-pyridin-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (244)
    8-(2-tert-Butyl-5-methyl-2H-pyrazol-3-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (245)
    4-[8-(2-Methylsulfanyl-pyridin-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (246)
    Essigsäure 4-[8-(4-acetylamino-benzoyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-butylester,
    (247)
    [8-(4-Acetylamino-benzoyl)-3-benzyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (248)
    Essigsäure 4-[8-(2-ethylsulfanyl-pyridin-3-carbonyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-butylester,
    (249)
    4-[8-(4-Methyl-[1,2,3]thiadiazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (250)
    4-[1-Allyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzolsulfonamid,
    (251)
    4-(8-Cyclobutancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzoesäuremethylester,
    (252)
    Essigsäure 2-[1-allyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-2-oxo-ethylester,
    (253)
    8-(Biphenyl-4-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (254)
    [3-(2-Methylsulfanyl-ethyl)-2-oxo-8-propionyl-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (255)
    8-(Benzo[1,3]dioxole-5-carbonyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (256)
    1-Allyl-8-(biphenyl-4-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (257)
    [3-Benzyl-8-(biphenyl-4-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (258)
    [8-(3-Dimethylamino-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (259)
    3-(2-Oxo-8-pentanoyl-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzonitril,
    (260)
    4-(8-Cyclopentancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzoesäuremethylester,
    (261)
    4-[1-(2-Fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-4-oxo-butansäurethylester,
    (262)
    1-(2-Fluor-benzyl)-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (263)
    4-[8-(2-Chlor-pyridin-4-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (264)
    3-[8-(3,5-Bis-trifluormethyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (265)
    3-Benzyl-1-(2-fluor-benzyl)-8-(2-methoxy-benzoyl)-1,4,8-triazaspiro[4.5]decan-2-on,
    (266)
    8-(Benzo[1,2,5]oxadiazol-5-carbonyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (267)
    [3-Benzyl-2-oxo-8-(4-sulfamoyl-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (268)
    3-[2-Oxo-8-(3,4,5-trimethoxy-benzoyl)1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (269)
    Essigsäure 2-[1-(4-acetoxy-butyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-1,1-dimethyl-2-oxo-ethylester,
    (270)
    8-(6-Chlor-pyridin-3-carbonyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (271)
    8-(2-Ethoxy-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (272)
    1-Allyl-8-cyclopropancarbonyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (273)
    3-[3-Isopropyl-8-(2-methoxy-acetyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (274)
    4-(2-Oxo-8-phenylacetyl-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzoesäuremethylester,
    (275)
    Essigsäure 2-[1-(3-cyano-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-1-phenyl-ethylester,
    (276)
    1-(2-Fluor-benzyl)-8-(4-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (277)
    4-(8-Cyclohexancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzoesäuremethylester,
    (278)
    1-(2-Fluor-benzyl)-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (279)
    [3-Isobutyl-8-(3-methyl-butyryl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (280)
    1-Allyl-8-(3,3-dimethyl-butyryl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (281)
    1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(2-methylsulfanyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (282)
    [3-Isobutyl-8-(2-methyl-pentanoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (283)
    4-[8-(5-tert-Butyl-2-methyl-furan-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (284)
    (3-Benzyl-8-cyclopropancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl)-essigsäureethylester,
    (285)
    [3-Benzyl-8-(3-methyl-butyryl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (286)
    1-(2,6-Dichlor-benzyl)-8-(2,5-dimethyl-furan-3-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (287)
    1-Allyl-3-isopropyl-8-[2-(3-methoxy-phenyl)-acetyl]-1,4,8-triazaspiro[4.5]decan-2-on,
    (288)
    [8-(4-tert-Butyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]-essigsäureethylester,
    (289)
    3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-(2-phenoxy-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (290)
    (3-Benzyl-2-oxo-8-pentanoyl-1,4,8-triaza-spiro[4.5]dec-1-yl)-essigsäureethylester,
    (291)
    8-(2-Chlor-pyridin-4-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (292)
    [8-(3-Methyl-butyryl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (293)
    1-Allyl-3-(2-methylsulfanyl-ethyl)-8-pentafluorbenzoyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (294)
    1-(2-Fluor-benzyl)-8-(2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (295)
    8-(Benzo[1,2,5]oxadiazol-5-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (296)
    4-[8-(4-tert-Butyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester,
    (297)
    [3-Benzyl-2-oxo-8-(1-phenyl-5-propyl-1H-pyrazol-4-carbonyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (298)
    1-Allyl-3-isopropyl-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (299)
    3-[2-Oxo-8-(2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (300)
    8-(2-Dimethylamino-acetyl)-1-(3,5-dimethyl-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (301)
    Essigsäure 4-[8-(2-ethoxy-benzoyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-butylester,
    (302)
    1-(2-Fluor-benzyl)-8-(3-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (303)
    [8-(Furan-2-carbonyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (304)
    8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (305)
    1-(2-Fluor-benzyl)-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (306)
    [3-Benzyl-8-(2-fluor-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (307)
    [8-(Isoxazol-5-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (308)
    1-(2,6-Dichlor-benzyl)-3-isobutyl-8-(4-propyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (309)
    [8-[2-(2,5-Dimethoxy-phenyl)-acetyl]-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (310)
    (3-Benzyl-8-cyclobutancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl)-essigsäureethylester,
    (311)
    1-(2-Fluor-benzyl)-8-[2-(4-methoxy-phenyl)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on,
    (312)
    1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (313)
    [3-(2-Methylsulfanyl-ethyl)-2-oxo-8-(4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (314)
    1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(1-phenyl-5-propyl-1H-pyrazol-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (315)
    1-(2,6-Dichlor-benzyl)-8-(2,3-difluor-4-methyl-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (316)
    1-Allyl-3-isopropyl-8-(2-methyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (317)
    8-(2-Chlor-5-trifluormethyl-benzoyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (318)
    1-Allyl-8-[2-(3-methoxy-phenyl)-acetyl]-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (319)
    1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (320)
    [3-Benzyl-8-(2-benzyloxy-acetyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (321)
    1-Allyl-8-(5-tert-butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (322)
    Essigsäure 1,1-dimethyl-2-[3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-ethylester,
    (323)
    Benzoesäure 2-[1-ethoxycarbonylmethyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester,
    (324)
    1-Allyl-3-isopropyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (325)
    1-Allyl-8-(2,5-dimethyl-furan-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (326)
    1-Allyl-8-(benzo[1,2,5]oxadiazol-5-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (327)
    1-(2-Fluor-benzyl)-8-(4-phenoxy-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (328)
    1-Allyl-8-(2-cyclopentyl-acetyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (329)
    [3-Benzyl-8-(naphthalin-2-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (330)
    8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (331)
    3-[8-(3,5-Dimethoxy-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (332)
    3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-(1-phenyl-5-propyl-1H-pyrazol-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (333)
    {3-Benzyl-8-[3-(2-chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl}-essigsäureethylester,
    (334)
    1-(2-Fluor-benzyl)-8-(3-fluor-4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (335)
    [8-[1-(4-Chlor-phenyl)-5-trifluormethyl-1H-pyrazol-4-carbonyl]-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (336)
    3-[8-(Naphthalin-1-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (337)
    [8-(3,3-Dimethyl-butyryl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (338)
    8-Acetyl-3-(2-methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (339)
    [3-Benzyl-8-(3-cyano-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (340)
    8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (341)
    4-[3-Benzyl-1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzonitril,
    (342)
    4-[3-Benzyl-1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-4-oxo-butyrsäure methylester,
    (343)
    3-(2-Methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (344)
    [3-Benzyl-8-(isoxazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (345)
    8-(3-Difluormethylsulfanyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (346)
    [3-Benzyl-8-(2,3-dimethyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (347)
    1-(2-Fluor-benzyl)-8-(4-propyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (348)
    3-[8-(4-Iod-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (349)
    1-(2-Fluor-benzyl)-8-(2-propyl-pentanoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (350)
    3-[8-(2,6-Difluor-3-methyl-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (351)
    3-(2-Methylsulfanyl-ethyl)-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (352)
    Essigsäure 4-[3-isobutyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-butylester,
    (353)
    8-[2-(4-Chlor-phenoxy)-acetyl]-3-(2-methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (354)
    [3-Benzyl-2-oxo-8-(3-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (355)
    8-(4-Brom-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (356)
    [8-(2-Chlor-pyridin-4-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (357)
    1-Allyl-8-(3,5-dimethoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (358)
    3-[8-(4-Methyl-3-nitro-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (359)
    8-(4-tert-Butyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (360)
    1-Allyl-3-isopropyl-8-(5-methyl-isoxazol-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (361)
    1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (362)
    [3-Benzyl-8-(3-cyclopentyl-propionyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (363)
    3-Benzyl-8-(3,5-difluor-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (364)
    [3-Benzyl-8-(5-fluor-2-trifluormethyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (365)
    [3-Benzyl-2-oxo-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (366)
    Benzoesäure 2-[1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester,
    (367)
    1-(2-Fluor-benzyl)-8-(2-methyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (368)
    1-(2-Fluor-benzyl)-8-(2-phenyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (369)
    1-Allyl-8-(6-chlor-pyridin-3-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (370)
    [8-(2,5-Dimethyl-furan-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (371)
    [8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (372)
    Benzoesäure 2-[1-allyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester,
    (373)
    Essigsäure 2-[1-allyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-1-phenyl-ethylester,
    (374)
    3-[8-(2-Chlor-6-fluor-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (375)
    3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (376)
    3-[8-(2,3-Dimethyl-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (377)
    [8-(5-Fluor-2-trifluormethyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (378)
    [8-Cyclopentancarbonyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (379)
    [3-(2-Methylsulfanyl-ethyl)-2-oxo-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (380)
    1-Allyl-8-[1-(4-chlor-phenyl)-5-trifluormethyl-1H-pyrazol-4-carbonyl]-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (381)
    1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(naphthalin-1-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (382)
    1-(2-fluor-benzyl)-8-(4-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (383)
    3-Benzyl-8-(2-benzyloxy-acetyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (384)
    3-[8-(2-chlor-6-fluor-3-methyl-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (385)
    1-Allyl-8-(2-chlor-5-trifluormethyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (386)
    8-(3-Methyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (387)
    1-(3,5-Dimethyl-benzyl)-8-(2-ethyl-butyryl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (388)
    8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (389)
    Benzoesäure 2-[1-(3-cyano-benzyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester,
    (390)
    8-(4-Methyl-3-nitro-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (391)
    1-(2,6-Dichlor-benzyl)-3-isobutyl-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (392)
    3-{8-[2-(2-Brom-phenyl)-acetyl]-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl}-benzonitril,
    (393)
    3-[8-(2,3-Dichlor-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (394)
    1-Allyl-8-(6-chlor-2H-chroman-3-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (395)
    {3-Benzyl-8-[2-(4-methoxy-phenyl)-acetyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl}-essigsäureethylester,
    (396)
    3-[3-Isopropyl-2-oxo-8-(1-phenyl-5-propyl-1H-pyrazol-4-carbonyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (397)
    8-(3-Cyclopentyl-propionyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (398)
    1-Allyl-8-(3-difluormethylsulfanyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (399)
    3-[8-(2-chlor-4-nitro-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (400)
    [8-(2-Ethoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (401)
    8-(2,5-Bis-trifluormethyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (402)
    8-(2-Chlor-pyridin-4-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (403)
    {3-Benzyl-8-[3-(2,6-dichlor-phenyl)-5-methyl-isoxazol-4-carbonyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl}-essigsäureethylester,
    (404)
    1-(3,5-Dimethyl-benzyl)-3-isobutyl-8-(2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (405)
    8-(3,5-Dimethoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (406)
    Benzoesäure 2-[3-benzyl-1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester,
    (407)
    3-[8-(Benzo[1,2,5]oxadiazol-5-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (408)
    [3-(2-Methylsulfanyl-ethyl)-2-oxo-8-(4-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (409)
    1-Allyl-3-isopropyl-8-[2-(4-methoxy-phenyl)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on,
    (410)
    3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-(4-propyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (411)
    3-Benzyl-8-(4-tert-butyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (412)
    1-Allyl-8-(2,6-difluor-3-methyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (413)
    8-(3,5-Bis-trifluormethyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (414)
    3-[8-(4-Iod-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (415)
    3-(2-Methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (416)
    [3-Benzyl-8-(2-chlor-pyridin-4-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (417)
    [3-(2-Methylsulfanyl-ethyl)-8-(4-nitro-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (418)
    8-(2-Ethyl-hexanoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (419)
    1-(2,6-Dichlor-benzyl)-3-isobutyl-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (420)
    [3-Benzyl-8-(2-chlor-4-nitro-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (421)
    3-Benzyl-8-(3,5-bis-trifluormethyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (422)
    [3-Benzyl-8-(4-brom-3-methyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (423)
    8-Cyclohexancarbonyl-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (424)
    8-(2,5-Dimethyl-furan-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (425)
    8-(3-Difluormethylsulfanyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (426)
    8-(Furan-2-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (427)
    [3-Benzyl-8-(2,3-difluor-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (428)
    3-[3-Isopropyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (429)
    3-[8-(3-Chlor-2-fluor-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (430)
    [3-Benzyl-8-(naphthalin-1-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (431)
    8-(4-tert-Butyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (432)
    3-[3-Benzyl-1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzonitril,
    (433)
    1-(2,6-Dichlor-benzyl)-8-(furan-2-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (434)
    8-(2,6-Dichlor-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (435)
    1-(3,5-Dimethyl-benzyl)-8-(3-fluor-4-trifluormethyl-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (436)
    1-(2-Fluor-benzyl)-8-(3-fluor-4-methyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (437)
    1-Allyl-8-(3-cyclopentyl-propionyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (438)
    8-[2-(3-Chlor-phenoxy)-acetyl]-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (439)
    1-(3,5-Dimethyl-benzyl)-3-isobutyl-8-(2-methylsulfanyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (440)
    3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-propionyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (441)
    3-[8-(3,4-Dimethoxy-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (442)
    3-(2-Methylsulfanyl-ethyl)-8-(naphthalin-2-carbonyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (443)
    8-(6-Chlor-2H-chroman-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (444)
    {3-Benzyl-2-oxo-8-[3-(3-trifluormethyl-phenyl)-acryloyl]-1,4,8-triaza-spiro[4.5]dec-1-yl}-essigsäureethylester,
    (445)
    1-(3,5-Dimethyl-benzyl)-3-isobutyl-8-(3-phenyl-acryloyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (446)
    3-[3-Isopropyl-2-oxo-8-(2-phenoxy-propionyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (447)
    3-[3-Isopropyl-2-oxo-8-(4-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril,
    (448)
    1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(3-nitro-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (449)
    [3-Benzyl-8-(3,4-dichlor-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester,
    (450)
    1-(2-Fluor-benzyl)-8-[3-(3-trifluormethyl-phenyl)-acryloyl]-1,4,8-triaza-spiro[4.5]decan-2-on,
    (451)
    1-Allyl-8-(3,5-bis-trifluormethyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (452)
    8-(3-Cyclopentyl-propionyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (453)
    1-(3,5-Dimethyl-benzyl)-3-isobutyl-8-(4-nitro-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    (454)
    8-(3-Cyclopentyl-propionyl)-1-(3,5-dimethyl-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on,
    (455)
    3-[3-Isopropyl-8-(isoxazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril und
    (456)
    3-Benzyl-1-(2-fluor-benzyl)-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on,
    jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihrer Racemate oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form entsprechender Salze, vorzugsweise Hydrochloride, oder jeweils in Form entsprechender Solvate.
Particularly preferred are substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I given above
Figure imgb0002
 wherein
R1 for a hydrogen radical, for a linear or branched, unsubstituted C1-4-Alkyl radical, for a linear or branched, unsubstituted C2-5Alkenyl radical, for a linear or branched, unsubstituted C2-3Alkynyl radical, a phenyl or naphthyl radical which is unsubstituted or mono- or polysubstituted by identical or different substituents selected from the group consisting of F, Cl, Br, -CN, -NO2, C1-5Alkyl, C1-5Alkoxy, -C (= O) -C1-5-Alkyl, -C (= O) -O-C1-5Alkyl, -S (= O)2-C1-6-alkyl, -C (= O) -C1-5Perfluoroalkyl, -CF3, -CHF2 and -CH2F is substituted and / or via a - (CH2) -, - (CH2)2-, - (CH2)3- or - (CH2)2-O bridge is bound for one over one - (CH2) Group -C (= O) -OR5Residue or for one via a - (CH2) -, - (CH2)2-, - (CH2)3- or - (CH2)4Group bound -O-C (= O) -R6Rest stands,
R2 for a hydrogen radical, for a linear or branched, unsubstituted, optionally one or more sulfur atoms as a chain member C having1-5Alkyl radical or a phenyl radical, wherein the phenyl radical is mono- or polysubstituted, identical or different, with a substituent selected from the group consisting of F, Cl, Br, -CN, -NO2, C1-5Alkyl, C1-5Alkoxy, -C (= O) -C1-5-Alkyl, -C (= O) -O-C1-5Alkyl, -S (= O)2-C1-6-alkyl, -C (= O) -C1-5Perfluoroalkyl, -CF3, CHF2 and CH2F is substituted and / or via a - (CH2) Bridge,
R3 for a hydrogen radical, for a biphenyl radical which has a - (CH2) -, - (CH2)2- or - (CH2)3Bridge, or for a C (= O) -R4Group stands,
R4 is a radical which is selected from the group consisting of methyl, ethyl, isopropyl, n-propyl, sec-butyl, isobutyl, tert-butyl, n-butyl, n-pentyl, 1-methylbutyl, 2-dimethyl propyl, 1-ethyl-propyl, 1-propyl-butyl, 1-ethyl-pentyl, dimethylaminomethyl, -CH2-CH2-CH = CH2, -CH2-O-CH3, -CH2-O-CH2-CH2-O-CH3, - CH2-CH2-Phenyl, -CH2-O-phenyl, -CH2-O-CH2-Phenyl, -CH2-CH2-CH2-O-phenyl, - C (H) (phenyl) (C2H5), -C (H) (CH3) -O-phenyl, -CH2-CH2- (C = O) -CH3, -CH2-O- (C = O) -CH3, -CH2-CH2- (C = O) -O-C2H5, -CH2-O- (C = O) -phenyl, -CH2- (C = O) -O-CH2-CH3, -C (H) (phenyl) - (C = O) -CH3, -C (H) (phenyl) -O- (C = O) -CH3, - C (CH3)2-O- (C = O) -CH3, -C (H) (NH- (C = O) -O- (CH3)3) (CH2-O-CH2-Phenyl), -C (CH3)2-CH2-COOH, unsubstituted phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-Chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-bromo-phenyl, 3-bromo-phenyl, 4-bromo-phenyl, 2-iodo-phenyl, 3-iodo-phenyl , 4-iodo-phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-n-propylphenyl , 3-n-propyl-phenyl, 4-n-propyl-phenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 2-methoxyphenyl, 3 Methoxy-phenyl, 4-methoxy-phenyl, 2-ethoxy-phenyl, 3-ethoxy-phenyl, 4-ethoxy-phenyl, 2-trifluoromethyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 2-trifluoromethoxy phenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-CF3-S-phenyl, 3-CF3-S-phenyl, 4-CF3-S-phenyl, 2-cyano-phenyl, 3-cyano-phenyl, 4-cyano-phenyl, 2-nitrophenyl, 3-nitro-phenyl, 4-nitro-phenyl, 2-CHF2-S-phenyl, 3-CHF2-S-phenyl, 4-CHF2-S-phenyl, 2-dimethylamino-phenyl, 3-dimethylamino-phenyl, 4-dimethylaminophenyl, 2-phenyl- (C = O) -O-CH 2 -phenyl, 3-phenyl- (C = O) -O-CH2-phenyl, 4-phenyl- (C = O) -O-CH2-phenyl, 2-CH3- (C = O) -NH-phenyl, 3-CH3- (C = O) -NH-phenyl, 4-CH3- (C = O) -NH-phenyl, 2-phenyl-phenyl, 3-phenyl-phenyl, 4-phenyl-phenyl, 2-NH2-SO2-Phenyl, 3-NH2-SO2-Pheny, 4-NH2-SO2-Phenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,3-dimethylphenyl, 2,3-dichlorophenyl, 3 , 4-dichlorophenyl, 2,6-dichlorophenyl, 2,3-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, pentafluorophenyl, 2-chloro-6-fluorophenyl, 4-bromo-3 -methyl-phenyl, 3-fluoro-4-methyl-phenyl, 3-chloro-2-fluoro-phenyl, 2-chloro-4-nitro-phenyl, 5-fluoro-2-trifluoromethyl-phenyl, 3-fluoro-4 trifluoromethyl, 4-methyl-3-nitro-phenyl, 2-chloro-5-trifluoro-methyl, 2,5-bis-trifluoromethyl-phenyl, 3,5-bis-trifluoromethyl-phenyl, 2-chloro-6-fluoro 3-methyl-phenyl, 6-chloro-2-fluoro-3-methylphenyl, 2,6-difluoro-4-methyl-phenyl, 2,6-difluoro-3-methyl-phenyl, 3,4,5-trimethoxy -phenyl, 2,3-difluoro-4-methyl-phenyl, 2-fluoro-benzyl, 3-fluoro-benzyl, 4-fluoro-benzyl, 2-chloro-benzyl, 3-chloro-benzyl, 4-chloro-benzyl , 2-Bromo-benzyl, 3-bromo-benzyl, 4-bromo-benzyl, 2-methyl-benzyl, 3-methyl-benzyl, 4-methyl-benzyl, 2-methoxy-benzyl, 3-methoxy-benzyl, 4 Methoxybenzyl, 3,4-dimethoxybenzyl, 2.5- Dimethoxy-benzyl, - CH = CH-phenyl, wherein the phenyl radical in the 2-, 3- or 4- position single or multiple, identical or different, with a radical selected from the group consisting of F, Cl, Br and CF3 may be substituted, -CH2-O-phenyl, wherein the phenyl radical in the 2, 3 or 4 position is mono- or polysubstituted, identical or different, with a radical selected from the group consisting of F, Cl, Br and CF.3 1-naphthyl, 2-naphthyl, 2-thienyl, 3-thienyl, 3-chlorothien-2-yl, 2-furanyl, 3-furanyl, 2,5-dimethyl-furan-3-yl, 5- tert-butyl-2-methyl-furan-3-yl, Pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 2-chloro-pyridin-4-yl, 6-chloro-pyridin-3-yl, 2-chloro-pyridin-3-yl, 2 Ethylsulfanylpyridin-3-yl, 2-phenoxypyridin-3-yl, 2-methylsulfanylpyridin-3-yl, 2-methyl-6-trifluoromethylpyridin-3-yl, isoxazol-5-yl, 5- Methyl-isoxazol-3-yl, 3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazol-4-yl, 3- (2-chloro-phenyl) -5-methyl-isoxazol-4 yl, 3- (2,6-dichloro-phenyl) -5-methyl-isoxazol-4-yl, 5-tert-butyl-2-methyl-2H-pyrazol-3-yl, 1-phenyl-5-n -Propyl-1H-pyrazol-4-yl, 1- (4-chloro-phenyl) -5-trifluoromethyl-1H-pyrazol-4-yl, 2-tert-butyl-5-methyl-2H-pyrazol-3-yl , 5-Methyl-2-phenyl-2H- [1,2,3] triazol-4-yl, 4-methyl- [1,2,3] thiadiazol-5-yl, 2-chloro-4-trifluoromethyl-pyrimidine -5-yl, 2-chloro-4-trifluoromethyl-pyrimidin-5-yl, benzo [1,2,5] oxadiazol-5-yl, benzo [1,3] dioxol-5-yl, 6-chloro-2H-chroman 3-yl, imidazolidine-2,4-dione-5-yl-methyl, cyclopropyl, cyclobutyl, optionally via a - (CH2) - or - (CH2)2Bridge bonded cyclopentyl, cyclohexyl, 4,7,7-trimethyl-3-oxo-2-oxabicyclo [2.2.1] heptyl and adamantyl.
Preferably, compounds of the above formula I, in which
  • A)
    R 1 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 hydroxyalkyl, C 2-6 alkenyl, C 2 -6- alkynyl radical, a phenyl radical or a mono-, di- or trisubstituted phenyl-substituted C 1-6 -alkyl radical,
    R 2 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 hydroxyalkyl, C 2-5 alkenyl, C 2 -6- alkynyl radical, a phenyl radical, a mono-, di- or trisubstituted by a phenyl radical substituted C 1-6 alkyl radical, an -OC 1-6 alkanoyl radical, an OH radical, a -O-C 1-6 alkyl, -OC 1-6 alkoxy, -OC 2-6 hydroxyalkyl, -OC 2-6 alkenyl, -OC 2-6 Alkynyl radical, an -O-phenyl radical or a mono-, di- or trisubstituted phenyl radical -OC 1-6 -alkyl radical,
    R 3 is a hydrogen radical, a C 1-6 alkyl radical, a C 2-6 alkenyl radical, a C 2-6 alkynyl radical, a C 3-7 cycloalkyl radical, a 1-6 halogen atoms substituted C 1-6 -alkyl radical, a hydroxyC 1-6 -alkyl radical, a C 1-6 -alkoxy radical, a C 1-6 -alkylthio radical, a C 1-6 -alkoxy radical C 1-6 alkyl, carboxy C 1-6 alkyl, (C 1-6 alkoxy) carbonyl C 1-6 alkyl, amino C 1-6 alkyl Radical, a mono (C 1-6 alkyl) amino radical, a di (C 1-6 alkyl) amino radical, a 2-oxopyrrolidin-1-ylmethyl radical, an aryl Radical, a diarylmethylol radical, a C 1-6 -alkyl radical substituted by one or two aryl radicals, a C 1-6 -alkanoyl radical or an arylcarbonyl radical, where each aryl is an unsubstituted phenyl radical Radical or represents a phenyl radical which is substituted by 1-3 substituents selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 alkoxy and CF 3 , and their physiologically acceptable salts, enantiomers and racemates,
    and or
  • B)
    the radicals R 1 , R 2 and R 3 each represent a hydrogen radical or a hydrocarbon radical and in each case their salts
    except.
    Very particular preference is given to substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the abovementioned general formula I selected from the group consisting of
    (1)
    3- ( S ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (2)
    8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (3)
    3- ( S , R ) -Benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (4)
    8-acetyl-3- ( S ) -benzyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (5)
    3- ( S, R ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (6)
    3- ( S ) -benzyl-8- (4-chlorobenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (7)
    8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (8th)
    1,3- ( S ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (9)
    8-Acetyl-1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (10)
    3- ( S , R ) -Benzyl-8- (4-chlorobenzoyl) -1- (4-methoxybenzyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (11)
    3- ( S , R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-fluoro-benzyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (12)
    1,3- ( S , R ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decane-2-one,
    (13)
    3- ( S , R ) -Benzyl-8- (2-ethyl-butyryl) -1- (4-methoxybenzyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (14)
    3- ( S , R ) -Benzyl-8- (2-ethylbutyryl) -1- (4-fluorobenzyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (15)
    1,3- ( S , R ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (16)
    1-Benzyl-8- (2-ethylbutyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (17)
    1,3- ( S ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (18)
    1,3- ( S ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (19)
    8-Acetyl-1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (20)
    3- ( S , R ) -Benzyl-8- (4-chlorobenzoyl) -1- (4-methoxybenzyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (21)
    3- ( S , R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-fluoro-benzyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (22)
    1,3- ( S , R ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (23)
    3- ( S , R ) -Benzyl-8- (2-ethyl-butyryl) -1- (4-methoxybenzyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (24)
    3- ( S , R ) -Benzyl-8- (2-ethylbutyryl) -1- (4-fluorobenzyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (25)
    1,3- ( S , R ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (26)
    1-Benzyl-8- (2-ethylbutyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (27)
    1,3- ( S ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (28)
    1-Benzyl-8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (29)
    1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (30)
    1-Benzyl-3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (31)
    1,3- ( S ) -dibenzyl-8-butyryl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (32)
    1,3 ( S ) -dibenzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (33)
    1,3- ( S ) -dibenzyl-8- (2,3-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (34)
    1,3- ( S ) -dibenzyl-8- [2- (4-chloro-phenoxy) -acetyl] -1,4,8-triazaspiro [4.5] decan-2-one,
    (35)
    1,3- ( S ) -dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (36)
    1,3- ( S ) -dibenzyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (37)
    1,3- ( S ) -dibenzyl-8- (3-phenylpropionyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (38)
    1,3- ( S ) -dibenzyl-8- (naphthalene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (39)
    1,3- ( S ) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (40)
    1,3- ( S ) -dibenzyl-8- (3-methoxybenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (41)
    1,3- ( S ) -dibenzyl-8- (4-fluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (42)
    1-Benzyl-8- (4-fluoro-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (43)
    1,3- ( S ) -dibenzyl-8-butyryl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (44)
    1,3- ( S ) -dibenzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (45)
    1,3- ( S ) -dibenzyl-8- (2,3-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (46)
    1,3- ( S ) -dibenzyl-8- [2- (4-chloro-phenoxy) -acetyl] -1,4,8-triazaspiro [4.5] decan-2-one,
    (47)
    1,3- ( S ) -dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (48)
    1,3- ( S ) -dibenzyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (49)
    1,3- ( S ) -dibenzyl-8- (3-phenylpropionyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (50)
    1,3- ( S ) -dibenzyl-8- (naphthalene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (51)
    1,3- ( S ) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (52)
    1,3- ( S ) -dibenzyl-8- (3-methoxybenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (53)
    1,3- ( S ) -dibenzyl-8- (4-fluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (54)
    1-Benzyl-8- (4-fluoro-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (55)
    N- [4- (3-isobutyl-2-oxo-1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-8-carbonyl) -phenyl] -acetamide,
    (56)
    1- (2-phenoxy-ethyl) -8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (57)
    2- (2-Oxo-8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzonitrile,
    (58)
    8- (2,4-dimethoxy-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (59)
    2- [8- (2-ethyl-butyryl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (60)
    4- (2-isobutyl-3-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl) -benzonitrile,
    (61)
    8- (6-chloro-pyridine-3-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (62)
    2- [8- (2-methyl-pentanoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (63)
    1-Benzyl-8- (biphenyl-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (64)
    3-isobutyl-8- (5-methyl-isoxazol-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (65)
    3-oxo-3- [2-oxo-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] dec-8-yl] -propionic acid ethyl ester,
    (66)
    8- (2-chloro-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (67)
    8-Cyclopentanecarbonyl-3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (68)
    8- (furan-2-carbonyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (69)
    3-Benzyl-8- (2-ethylsulfanyl-pyridine-3-carbonyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (70)
    3-Benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (71)
    8- (2-benzyloxy-acetyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (72)
    3-Benzyl-8- (2-methoxy-acetyl) -1-prop-2-ynyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (73)
    8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3-isobutyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (74)
    2- {8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec-1 ylmethyl} -benzonitrile,
    (75)
    3-Benzyl-8- (2-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (76)
    3-Benzyl-8- (3-dimethylamino-benzoyl) -1-methyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (77)
    8- (3-methyl-benzoyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (78)
    3-isopropyl-1- (3-methyl-but-2-enyl) -8- (pyridin-4-carbonyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (79)
    1-Benzyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (80)
    2- {8- [3- (2-chloro-phenyl) acryloyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl} -benzonitrile,
    (81)
    8- (3-chloro-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (82)
    Acetic acid 2- (2-benzyl-3-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl) -2-oxo-1-phenylethyl ester,
    (83)
    8- (3,5-dimethoxy-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (84)
    3-Benzyl-8- (isoxazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (85)
    8- (3-chloro-thiophene-2-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (86)
    Of 3-isopropyl-8-pentafluorobenzoyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (87)
    8- (2,5-dimethyl-furan-3-carbonyl) -3-isobutyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (88)
    1-Butyl-8- [2- (3,4-dimethoxy-phenyl) -acetyl] -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (89)
    1-Benzyl-3-isopropyl-8- (pyridin-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (90)
    1,3-dibenzyl-8- (3-dimethylamino-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (91)
    5- {2- [1- (4-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -2 oxo-ethyl} imidazolidine-2,4-dione,
    (92)
    8- (biphenyl-4-carbonyl) -1- (4-fluoro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (93)
    2- [2-oxo-8- (2-propyl-pentanoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (94)
    2- [8- (Furan-2-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (95)
    8- [2- (4-chloro-phenoxy) -acetyl] -3-isobutyl-1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (96)
    1,3-dibenzyl-8- (4-bromo-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (97)
    8- (3-Difluormethylsulfanyl-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (98)
    8- (2,3-dimethyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (99)
    3-Benzyl-8- (2,3-dimethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (100)
    1- (4-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -8- (pyridine-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (101)
    3-Benzyl-8- (3,3-dimethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (102)
    2- [8- (3-dimethylamino-benzoyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (103)
    3- [8- (2-methoxy-acetyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (104)
    Acetic acid 2- (3-benzyl-1-methyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl) -2-oxo-1-phenylethyl ester,
    (105)
    2- [8- [2- (2-methoxy-ethoxy) -acetyl] -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl ] -benzonitrile,
    (106)
    3-benzyl-8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -1,4,8-triaza-spiro [4.5] decan-2-one,
    (107)
    8- (2-chloro-6-fluoro-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (108)
    1-methyl-3- (2-methylsulfanyl-ethyl) -8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (109)
    8- (2-chloro-pyridine-3-carbonyl) -1- (4-fluoro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (110)
    8- (2-ethyl-butyryl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (111)
    1-methyl-3- (2-methylsulfanyl-ethyl) -8- (2-phenoxy-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (112)
    8- (3-fluoro-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (113)
    3-benzyl-8- (naphthalene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (114)
    8-Cyclohexanecarbonyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (115)
    8- (2-phenoxy-acetyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (116)
    4- [1-Butyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl] -benzonitrile,
    (117)
    3-Benzyl-8- (3,3-dimethyl-butyryl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (118)
    3-Benzyl-8- (4-propyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (119)
    3-isopropyl-8- (2-phenoxy-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (120)
    1-Butyl-8-hexanoyl-3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (121)
    8- (4-bromo-3-methyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (122)
    8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza spiro [4.5] decan-2-one,
    (123)
    1- (2-fluoro-benzyl) -3-isobutyl-8- (3-methyl-benzoyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (124)
    8- (2-ethyl-hexanoyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (125)
    3-Benzyl-8- (3,4-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (126)
    3-Benzyl-8- (4-ethoxy-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (127)
    1-Benzyl-8- (6-chloro-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (128)
    8- (3-Dimethylamino-benzoyl) -1- (3,5-dimethyl-benzyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (129)
    3- [8- (Benzo [1,3] dioxole-5-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl ] -benzonitrile,
    (130)
    3-benzyl-1-methyl-8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (131)
    8- (4-ethoxy-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (132)
    3-Benzyl-8- (2-benzyloxy-acetyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan2-one,
    (133)
    8- (3,4-difluoro-benzoyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (134)
    3-benzyl-1-methyl-8- (2-methylsulfanyl-pyridine-3-carbonyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (135)
    1-butyl-8- (4-methoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (136)
    1,3-dibenzyl-8- (2-ethylsulfanyl-pyridine-3-carbonyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (137)
    3-Benzyl-8- (3-difluormethylsulfanyl-benzoyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (138)
    1- (4-fluoro-benzyl) -8- (furan-2-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (139)
    3-Benzyl-8- (3-fluoro-4-methyl-benzoyl) -1-methyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (140)
    8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (141)
    1-butyl-8- (6-chloro-2H-chroman-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (142)
    3- [8- (3-methoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triazaspiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (143)
    8-cyclobutanecarbonyl-3- (2-methylsulfanyl-ethyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (144)
    3-Benzyl-1-butyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (145)
    1-Benzyl-8- (3-chloro-thiophene-2-carbonyl) -3-isobutyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (146)
    3-Benzyl-8- (2,5-bis-trifluoromethyl-benzoyl) -1-butyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (147)
    8- (3-chloro-2-fluoro-benzoyl) -1- (3,5-dimethyl-benzyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decane 2-one,
    (148)
    1-Benzyl-8- (2-chloro-pyridine-3-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (149)
    3-Isobutyl-8-pentafluorobenzoyl-1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (150)
    8- (2-benzyloxy-acetyl) -1-butyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (151)
    8- (furan-2-carbonyl) -3-isobutyl-1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (152)
    1-Butyl-3- (2-methylsulfanyl-ethyl) -8- (4-phenoxy-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (153)
    3-Benzyl-8- (6-chloro-pyridine-3-carbonyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (154)
    1- (2-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -8- (2-phenoxy-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2- on,
    (155)
    1- (2-fluoro-benzyl) -3-isobutyl-8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (156)
    8- [2- (3-chloro-phenoxy) -acetyl] -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (157)
    8- (2,3-dimethyl-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (158)
    3-isopropyl-8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (159)
    3-benzyl-1-methyl-8- (5-methyl-2-phenyl-2H- [1,2,3] triazole-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2 -one
    (160)
    8- [3- (2-chloro-phenyl) -5-methyl-isoxazole-4-carbonyl] -1- (3,5-dimethyl-benzyl) -3- (2-methylsulfanyl-ethyl) -1,4, 8-triaza-spiro [4.5] decan-2-one,
    (161)
    1- (2-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -8- (pyridine-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (162)
    1-Benzyl-3- (2-methylsulfanyl-ethyl) -8- (2-phenoxy-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (163)
    1,3-dibenzyl-8- (3-chloro-thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (164)
    3-Benzyl-8- (4-tert-butyl-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (165)
    2- [3-isobutyl-8- (2-methoxy-acetyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (166)
    3-Benzyl-1-butyl-8- (5-fluoro-2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (167)
    3-benzyl-8- [2- (4-methoxy-phenyl) -acetyl] -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (168)
    1,3-dibenzyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (169)
    1-Benzyl-3-isopropyl-8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (170)
    1-Benzyl-8- (4-ethoxy-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (171)
    3-Benzyl-1-butyl-8-cyclohexanecarbonyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (172)
    3- [8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8 -triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (173)
    1- (2-fluoro-benzyl) -3-isobutyl-8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (174)
    1-methyl-3- (2-methylsulfanyl-ethyl) -8- (2-propyl-pentanoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (175)
    3-benzyl-1-methyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (176)
    3-isobutyl-1-prop-2-ynyl-8- (3-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (177)
    3-Benzyl-8- (furan-2-carbonyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (178)
    1-methyl-3- (2-methylsulfanyl-ethyl) -8- (naphthalene-1-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (179)
    3-Benzyl-1-butyl-8- (3-cyclopentyl-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (180)
    1- (3,5-dimethyl-benzyl) -3- (2-methylsulfanyl-ethyl) -8-pentanoyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (181)
    3-Benzyl-1-butyl-8- (2-methoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (182)
    3-Benzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (183)
    1-Benzyl-8- (3-difluormethylsulfanyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (184)
    8- (2-chloro-6-fluoro-3-methyl-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (185)
    4- [3-isopropyl-8- (2-methylsulfanyl-pyridine-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (186)
    8- [2- (2,5-Dimethoxy-phenyl) -acetyl] -1- (2-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (187)
    8- (5-tert-Butyl-2-methyl-furan-3-carbonyl) -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2- on,
    (188)
    8- (2-cyclopentyl-acetyl) -1- (4-fluoro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (189)
    4- [8- (3,3-dimethyl-butyryl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (190)
    3- [8-Cyclopropanecarbonyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (191)
    3- [3- (2-methylsulfanyl-ethyl) -2-oxo-8- (3-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (192)
    1-butyl-8- (2-cyclopentyl-acetyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (193)
    3-Benzyl-1-butyl-8- (pyridin-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (194)
    3-benzyl-8- [3- (2-chloro-phenyl) acryloyl] -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (195)
    4- [8- (3-fluoro-4-trifluoromethyl-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (196)
    8- [3- (2,6-dichloro-phenyl) -5-methyl-isoxazole-4-carbonyl] -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [ 4.5] decan-2-one,
    (197)
    1-Butyl-8-cyclohexanecarbonyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (198)
    3-Benzyl-1-butyl-8- (4-iodo-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one
    (199)
    1-methyl-3- (2-methylsulfanyl-ethyl) -8- [3- (3-trifluoromethyl-phenyl) acryloyl] -1,4,8-triaza-spiro [4.5] decan-2-one,
    (200)
    1,3-dibenzyl-8- (4-phenoxy-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one
    (201)
    3-Benzyl-8- (2-chloro-6-fluoro-benzoyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (202)
    4- [8- (2-chloro-pyridine-3-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (203)
    8- (2,5-dimethyl-furan-3-carbonyl) -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (204)
    8- (biphenyl-4-carbonyl) -3- (2-methylsulfanyl-ethyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (205)
    8- (3-chloro-thiophene-2-carbonyl) -3- (2-methylsulfanyl-ethyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (206)
    1- (4-fluoro-benzyl) -8- [2- (4-methoxy-phenyl) -acetyl] -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decane 2-one,
    (207)
    1-Benzyl-3-isopropyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (208)
    2- [3-Isopropyl-8- (2-methylsulfanyl-pyridine-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (209)
    3- [8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl ] -benzonitrile,
    (210)
    1-butyl-8- (2,5-dimethyl-furan-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (211)
    8- (3-Cyclopentyl-propionyl) -1- (2-fluoro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (212)
    1-Benzyl-8- (3-cyclopentyl-propionyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (213)
    3- (2-methylsulfanyl-ethyl) -8- (4-phenoxy-butyryl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (214)
    1,3-dibenzyl-8- (3-phenyl-acryloyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (215)
    3-Benzyl-8- (6-chloro-2-fluoro-3-methyl-benzoyl) -1-methyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (216)
    8- [3- (2-chloro-phenyl) acryloyl] -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (217)
    2- [3-isopropyl-2-oxo-8- (3-phenyl-acryloyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (218)
    3-benzyl-1-methyl-8- (4-methyl-3-nitro-benzoyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (219)
    1-Benzyl-8- (furan-2-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (220)
    1-butyl-8- (3,5-dimethoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (221)
    1,3-dibenzyl-8- (3,3-dimethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (222)
    8- (2,6-difluoro-3-methyl-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (223)
    2- [8- (2-chloro-6-fluoro-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] - benzonitrile,
    (224)
    8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -3-isopropyl-1- (3-methyl-but-2-enyl) -1,4, 8-triaza-spiro [4.5] decan-2-one,
    (225)
    3-isobutyl-1-prop-2-ynyl-8- (4-trifluoromethoxy-benzoyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (226)
    1-Benzyl-8- (2-chloro-6-fluoro-3-methyl-benzoyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (227)
    Benzoic acid 2- (1-benzyl-3-isopropyl-2-oxo-1,4,8-triazaspiro [4.5] decane-8-carbonyl) benzyl ester,
    (228)
    1,3-dibenzyl-8- (2-phenyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (229)
    3-benzyl-1-methyl-8- (4-nitro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (230)
    3-benzyl-1-methyl-8- (5-methyl-isoxazol-3-carbonyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (231)
    1-Benzyl-8- (6-chloro-2-fluoro-3-methyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (232)
    1-Benzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -3-isobutyl-1,4,8-triazaspiro [4.5] decan-2-one,
    (233)
    3-Benzyl-8- (6-chloro-2H-chroman-3-carbonyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (234)
    3-Benzyl-1-butyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (235)
    3-Benzyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one .
    (236)
    2- [8- (6-chloro-2H-chroman-3-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (237)
    2- [8- (5-methyl-isoxazole-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] - benzonitrile,
    (238)
    2- [8- (3-chloro-2-fluoro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (239)
    4- [8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl ] benzoate,
    (240)
    3-Benzyl-1-butyl-8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (241)
    3-Benzyl-1-butyl-8- (2-chloro-4-trifluoromethyl-pyrimidine-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (242)
    3-benzyl-8- (5-methyl-isoxazole-3-carbonyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (243)
    4- [8- (2-chloro-pyridine-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (244)
    8- (2-tert-butyl-5-methyl-2H-pyrazole-3-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (245)
    4- [8- (2-methylsulfanyl-pyridine-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (246)
    Acetic acid 4- [8- (4-acetylaminobenzoyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -butyl ester,
    (247)
    [8- (4-acetylamino-benzoyl) -3-benzyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (248)
    Acetic acid 4- [8- (2-ethylsulfanylpyridine-3-carbonyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -butyl ester,
    (249)
    4- [8- (4-Methyl- [1,2,3] thiadiazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (250)
    4- [1-allyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl] -benzenesulfonamide,
    (251)
    4- (8-cyclobutanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzoic acid methyl ester,
    (252)
    Acetic acid 2- [1-allyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triazaspiro [4.5] dec-8-yl] -2-oxo-ethyl ester,
    (253)
    8- (biphenyl-4-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (254)
    [3- (2-methylsulfanyl-ethyl) -2-oxo-8-propionyl-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (255)
    8- (benzo [1,3] dioxole-5-carbonyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (256)
    1-Allyl-8- (biphenyl-4-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (257)
    [3-Benzyl-8- (biphenyl-4-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (258)
    [8- (3-dimethylamino-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (259)
    3- (2-oxo-8-pentanoyl-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzonitrile,
    (260)
    4- (8-cyclopentanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzoic acid methyl ester,
    (261)
    4- [1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -4-oxo-butansäurethylester,
    (262)
    1- (2-fluoro-benzyl) -8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (263)
    4- [8- (2-Chloro-pyridin-4-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (264)
    3- [8- (3,5-Bis-trifluoromethyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (265)
    3-benzyl-1- (2-fluoro-benzyl) -8- (2-methoxy-benzoyl) -1,4,8-triazaspiro [4.5] decan-2-one,
    (266)
    8- (Benzo [1,2,5] oxadiazol-5-carbonyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2- on,
    (267)
    [3-benzyl-2-oxo-8- (4-sulfamoyl-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (268)
    3- [2-oxo-8- (3,4,5-trimethoxy-benzoyl) 1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (269)
    Acetic acid 2- [1- (4-acetoxy-butyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -1,1-dimethyl-2-oxo ethyl,
    (270)
    8- (6-chloro-pyridine-3-carbonyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (271)
    8- (2-ethoxy-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (272)
    1-Allyl-8-cyclopropanecarbonyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (273)
    3- [3-Isopropyl-8- (2-methoxy-acetyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (274)
    4- (2-oxo-8-phenylacetyl-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzoic acid methyl ester,
    (275)
    Acetic acid 2- [1- (3-cyano-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -2-oxo-1-phenylethyl ester,
    (276)
    1- (2-fluoro-benzyl) -8- (4-methoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (277)
    4- (8-cyclohexanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzoic acid methyl ester,
    (278)
    1- (2-fluoro-benzyl) -8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (279)
    [3-isobutyl-8- (3-methyl-butyryl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (280)
    1-Allyl-8- (3,3-dimethyl-butyryl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (281)
    1-allyl-3- (2-methylsulfanyl-ethyl) -8- (2-methylsulfanyl-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (282)
    [3-isobutyl-8- (2-methyl-pentanoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (283)
    4- [8- (5-tert-Butyl-2-methyl-furan-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (284)
    (3-Benzyl-8-cyclopropanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl) -acetic acid ethyl ester,
    (285)
    [3-benzyl-8- (3-methyl-butyryl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (286)
    1- (2,6-dichloro-benzyl) -8- (2,5-dimethyl-furan-3-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (287)
    1-Allyl-3-isopropyl-8- [2- (3-methoxy-phenyl) -acetyl] -1,4,8-triazaspiro [4.5] decan-2-one,
    (288)
    [8- (4-tert-butyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triazaspiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (289)
    3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8- (2-phenoxy-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2- on,
    (290)
    (Spiro 3-benzyl-2-oxo-8-pentanoyl-1,4,8-triaza-[4.5] dec-1-yl) -acetic acid ethyl ester,
    (291)
    8- (2-Chloro-pyridin-4-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (292)
    [8- (3-methyl-butyryl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (293)
    1-allyl-3- (2-methylsulfanyl-ethyl) -8-pentafluorobenzoyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (294)
    1- (2-fluoro-benzyl) -8- (2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (295)
    8- (Benzo [1,2,5] oxadiazol-5-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (296)
    4- [8- (4-tert-Butyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester,
    (297)
    [3-benzyl-2-oxo-8- (1-phenyl-5-propyl-1H-pyrazole-4-carbonyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (298)
    1-Allyl-3-isopropyl-8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (299)
    3- [2-oxo-8- (2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (300)
    8- (2-Dimethylamino-acetyl) -1- (3,5-dimethyl-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (301)
    Acetic acid 4- [8- (2-ethoxy-benzoyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -butyl ester,
    (302)
    1- (2-fluoro-benzyl) -8- (3-methoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (303)
    [8- (furan-2-carbonyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (304)
    8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (305)
    1- (2-fluoro-benzyl) -8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (306)
    [3-Benzyl-8- (2-fluoro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (307)
    [8- (isoxazole-5-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (308)
    1- (2,6-dichloro-benzyl) -3-isobutyl-8- (4-propyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (309)
    [8- [2- (2,5-Dimethoxy-phenyl) -acetyl] -3- (2-methylsulfanyl-ethyl) dec-1-yl -2-oxo-1,4,8-triaza-spiro [4.5] ] acetic acid ethyl ester,
    (310)
    (3-Benzyl-8-cyclobutanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl) -acetic acid ethyl ester,
    (311)
    1- (2-fluoro-benzyl) -8- [2- (4-methoxy-phenyl) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one,
    (312)
    1-allyl-3- (2-methylsulfanyl-ethyl) -8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (313)
    [3- (2-methylsulfanyl-ethyl) -2-oxo-8- (4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (314)
    1-allyl-3- (2-methylsulfanyl-ethyl) -8- (1-phenyl-5-propyl-1H-pyrazole-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2- on,
    (315)
    1- (2,6-dichloro-benzyl) -8- (2,3-difluoro-4-methyl-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (316)
    1-Allyl-3-isopropyl-8- (2-methyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (317)
    8- (2-chloro-5-trifluoromethyl-benzoyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (318)
    1-Allyl-8- [2- (3-methoxy-phenyl) -acetyl] -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (319)
    1-allyl-3- (2-methylsulfanyl-ethyl) -8- (3-phenyl-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (320)
    [3-Benzyl-8- (2-benzyloxy-acetyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (321)
    1-Allyl-8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decane 2-one,
    (322)
    Acetic acid 1,1-dimethyl-2- [3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8- yl] -2-oxo-ethyl ester,
    (323)
    Benzoic acid 2- [1-ethoxycarbonylmethyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester,
    (324)
    1-Allyl-3-isopropyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (325)
    1-Allyl-8- (2,5-dimethyl-furan-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (326)
    1-Allyl-8- (benzo [1,2,5] oxadiazol-5-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (327)
    1- (2-fluoro-benzyl) -8- (4-phenoxy-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (328)
    1-Allyl-8- (2-cyclopentyl-acetyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (329)
    [3-benzyl-8- (naphthalene-2-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (330)
    8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (331)
    3- [8- (3,5-dimethoxy-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (332)
    3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8- (1-phenyl-5-propyl-1H-pyrazole-4-carbonyl) -1,4,8-triaza-spiro [ 4.5] decan-2-one,
    (333)
    {3-benzyl-8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec -1-yl} -acetic acid ethyl ester,
    (334)
    1- (2-fluoro-benzyl) -8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (335)
    [8- [1- (4-chloro-phenyl) -5-trifluoromethyl-1H-pyrazole-4-carbonyl] -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (336)
    3- [8- (naphthalene-1-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (337)
    [8- (3,3-dimethyl-butyryl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (338)
    8-Acetyl-3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (339)
    [3-Benzyl-8- (3-cyano-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (340)
    8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (341)
    4- [3-benzyl-1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl] -benzonitrile,
    (342)
    4- [3-Benzyl-1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4,5] dec-8-yl] -4-oxo-butyric acid methyl ester,
    (343)
    3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (344)
    [3-Benzyl-8- (isoxazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (345)
    8- (3-Difluormethylsulfanyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (346)
    [3-Benzyl-8- (2,3-dimethyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (347)
    1- (2-fluoro-benzyl) -8- (4-propyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (348)
    3- [8- (4-iodo-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (349)
    1- (2-fluoro-benzyl) -8- (2-propyl-pentanoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (350)
    3- [8- (2,6-difluoro-3-methyl-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (351)
    3- (2-methylsulfanyl-ethyl) -8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (352)
    Acetic acid 4- [3-isobutyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl ] butyl,
    (353)
    8- [2- (4-chloro-phenoxy) -acetyl] -3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2- on,
    (354)
    [3-benzyl-2-oxo-8- (3-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (355)
    8- (4-bromo-benzoyl) -3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (356)
    [8- (2-Chloro-pyridin-4-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (357)
    1-Allyl-8- (3,5-dimethoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (358)
    3- [8- (4-methyl-3-nitro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (359)
    8- (4-tert-butyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (360)
    1-Allyl-3-isopropyl-8- (5-methyl-isoxazol-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (361)
    1-allyl-3- (2-methylsulfanyl-ethyl) -8- (2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (362)
    [3-benzyl-8- (3-cyclopentyl-propionyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (363)
    3-Benzyl-8- (3,5-difluoro-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (364)
    [3-benzyl-8- (5-fluoro-2-trifluoromethyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (365)
    [3-benzyl-2-oxo-8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (366)
    Benzoic acid 2- [1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester,
    (367)
    1- (2-fluoro-benzyl) -8- (2-methyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (368)
    1- (2-fluoro-benzyl) -8- (2-phenyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (369)
    1-Allyl-8- (6-chloro-pyridine-3-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (370)
    [8- (2,5-dimethyl-furan-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] - acetate,
    (371)
    [8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec -1-yl] -acetic acid ethyl ester,
    (372)
    Benzoic acid 2- [1-allyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester,
    (373)
    Acetic acid 2- [1-allyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -2-oxo-1-phenylethyl ester .
    (374)
    3- [8- (2-chloro-6-fluoro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (375)
    3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8- (3-phenyl-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (376)
    3- [8- (2,3-dimethyl-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (377)
    [8- (5-fluoro-2-trifluoromethyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (378)
    [8-cyclopentanecarbonyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (379)
    [3- (2-methylsulfanyl-ethyl) -2-oxo-8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (380)
    1-allyl-8- [1- (4-chloro-phenyl) -5-trifluoromethyl-1H-pyrazole-4-carbonyl] -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [ 4.5] decan-2-one,
    (381)
    1-allyl-3- (2-methylsulfanyl-ethyl) -8- (naphthalene-1-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (382)
    1- (2-fluoro-benzyl) -8- (4-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (383)
    3-Benzyl-8- (2-benzyloxy-acetyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (384)
    3- [8- (2-chloro-6-fluoro-3-methyl-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (385)
    1-Allyl-8- (2-chloro-5-trifluoromethyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (386)
    8- (3-methyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (387)
    1- (3,5-dimethyl-benzyl) -8- (2-ethyl-butyryl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (388)
    8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza spiro [4.5] decan-2-one,
    (389)
    Benzoic acid 2- [1- (3-cyano-benzyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester,
    (390)
    8- (4-methyl-3-nitro-benzoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2- on,
    (391)
    1- (2,6-dichloro-benzyl) -3-isobutyl-8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (392)
    3- {8- [2- (2-bromo-phenyl) -acetyl] -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl} -benzonitrile,
    (393)
    3- [8- (2,3-dichloro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (394)
    1-Allyl-8- (6-chloro-2H-chroman-3-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (395)
    {3-benzyl-8- [2- (4-methoxy-phenyl) -acetyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl} -acetic acid ethyl ester,
    (396)
    3- [3-isopropyl-2-oxo-8- (1-phenyl-5-propyl-1H-pyrazole-4-carbonyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] - benzonitrile,
    (397)
    8- (3-Cyclopentyl-propionyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (398)
    1-Allyl-8- (3-difluormethylsulfanyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (399)
    3- [8- (2-chloro-4-nitro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (400)
    [8- (2-ethoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (401)
    8- (2,5-bis-trifluoromethyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (402)
    8- (2-Chloro-pyridin-4-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2- on,
    (403)
    {3-benzyl-8- [3- (2,6-dichloro-phenyl) -5-methyl-isoxazole-4-carbonyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec-1 yl} acetic acid ethyl ester,
    (404)
    1- (3,5-dimethyl-benzyl) -3-isobutyl-8- (2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (405)
    8- (3,5-dimethoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (406)
    Benzoic acid 2- [3-benzyl-1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester,
    (407)
    3- [8- (Benzo [1,2,5] oxadiazol-5-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (408)
    [3- (2-methylsulfanyl-ethyl) -2-oxo-8- (4-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (409)
    1-Allyl-3-isopropyl-8- [2- (4-methoxy-phenyl) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one,
    (410)
    3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8- (4-propyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (411)
    3-Benzyl-8- (4-tert-butyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (412)
    1-Allyl-8- (2,6-difluoro-3-methyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (413)
    8- (3,5-Bis-trifluoromethyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (414)
    3- [8- (4-iodo-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (415)
    3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (416)
    [3-Benzyl-8- (2-chloro-pyridin-4-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (417)
    [3- (2-methylsulfanyl-ethyl) -8- (4-nitro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (418)
    8- (2-ethyl-hexanoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (419)
    1- (2,6-dichloro-benzyl) -3-isobutyl-8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (420)
    [3-Benzyl-8- (2-chloro-4-nitro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (421)
    3-Benzyl-8- (3,5-bis-trifluoromethyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (422)
    [3-Benzyl-8- (4-bromo-3-methyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (423)
    8-cyclohexanecarbonyl-3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (424)
    8- (2,5-dimethyl-furan-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decane 2-one,
    (425)
    8- (3-Difluormethylsulfanyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (426)
    8- (furan-2-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (427)
    [3-Benzyl-8- (2,3-difluoro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (428)
    3- [3-isopropyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (429)
    3- [8- (3-chloro-2-fluoro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (430)
    [3-benzyl-8- (naphthalene-1-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (431)
    8- (4-tert-butyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (432)
    3- [3-benzyl-1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl] -benzonitrile,
    (433)
    1- (2,6-dichloro-benzyl) -8- (furan-2-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (434)
    8- (2,6-dichloro-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (435)
    1- (3,5-dimethyl-benzyl) -8- (3-fluoro-4-trifluoromethyl-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (436)
    1- (2-fluoro-benzyl) -8- (3-fluoro-4-methyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (437)
    1-Allyl-8- (3-cyclopentyl-propionyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (438)
    8- [2- (3-chloro-phenoxy) -acetyl] -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decane 2-one,
    (439)
    1- (3,5-dimethyl-benzyl) -3-isobutyl-8- (2-methylsulfanyl-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (440)
    3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8-propionyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (441)
    3- [8- (3,4-dimethoxy-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (442)
    3- (2-methylsulfanyl-ethyl) -8- (naphthalene-2-carbonyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (443)
    8- (6-chloro-2H-chroman-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decane 2-one,
    (444)
    {3-benzyl-2-oxo-8- [3- (3-trifluoromethyl-phenyl) acryloyl] -1,4,8-triaza-spiro [4.5] dec-1-yl} -acetic acid ethyl ester,
    (445)
    1- (3,5-dimethyl-benzyl) -3-isobutyl-8- (3-phenyl-acryloyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (446)
    3- [3-isopropyl-2-oxo-8- (2-phenoxy-propionyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (447)
    3- [3-isopropyl-2-oxo-8- (4-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile,
    (448)
    1-allyl-3- (2-methylsulfanyl-ethyl) -8- (3-nitro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (449)
    [3-Benzyl-8- (3,4-dichloro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester,
    (450)
    1- (2-fluoro-benzyl) -8- [3- (3-trifluoromethyl-phenyl) acryloyl] -1,4,8-triaza-spiro [4.5] decan-2-one,
    (451)
    1-Allyl-8- (3,5-bis-trifluoromethyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (452)
    8- (3-Cyclopentyl-propionyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (453)
    1- (3,5-dimethyl-benzyl) -3-isobutyl-8- (4-nitro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    (454)
    8- (3-Cyclopentyl-propionyl) -1- (3,5-dimethyl-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one,
    (455)
    3- [3-Isopropyl-8- (isoxazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile and
    (456)
    3-benzyl-1- (2-fluoro-benzyl) -8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one,
    in each case optionally in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of corresponding salts, preferably hydrochlorides, or in each case in the form of corresponding solvates.

Ein weiterer Gegenstand der vorliegenden Erfindung ist ein Verfahren zur Herstellung der erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen, gemäß dem ein geschütztes Piperidin-4-on der allgemeinen Formel 11,

Figure imgb0003
worin P für eine Schutzgruppe steht, durch Umsetzung mit wenigstens einer Verbindung der allgemeinen Formel III,
Figure imgb0004
 worin R2 die vorstehend genannte Bedeutung, in wenigstens eine Verbindung der allgemeinen Formel IV,
Figure imgb0005
 worin P und R2 die vorstehend genannte Bedeutung haben, überführt wird, welche ggf. gereinigt und/oder ggf. isoliert wird, und gegebenenfalls durch Umsetzung mit wenigstens einer Verbindung der allgemeinen Formel R1-X1, worin R1 die vorstehend genannte Bedeutung hat und X1 für eine geeignete Austrittsgruppe, vorzugsweise für einen Halogen-Rest, steht, ggf. in Gegenwart wenigstens einer Base, in wenigstens eine Verbindung der allgemeinen Formel V,
Figure imgb0006
 worin R1, R2 und P die vorstehend genannte Bedeutung haben, überführt wird, und diese ggf. gereinigt und/oder ggf. isoliert wird, und ggf. durch Abspaltung der Schutzgruppe P in wenigstens eine Verbindung der allgemeinen Formel VI,
Figure imgb0007
 überführt wird, diese ggf. gereinigt und/oder ggf. isoliert wird, und ggf. wenigstens eine Verbindung der allgemeinen Formel IV, V oder VI durch Umsetzung mit einem Carbonsäurederivat der allgemeinen Formel R4-(C=O)-X2, einem Carbonsäureanhydrid der allgemeinen Formel (R4-(C=O))2O oder einer Verbindung der allgemeinen Formel R3-X3, worin der Rest R3 die vorstehend genannte Bedeutung mit Ausnahme von Wasserstoff und -(C=O)-R4 hat, R4 jeweils die vorstehend genannte Bedeutung hat und X2 und X3 jeweils für eine geeignete Austrittsgruppe, vorzugsweise für einen Halogen-Rest, stehen, in wenigstens eine erfindungsgemäße substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung überführt wird, und diese Verbindung ggf. gereinigt und/oder ggf. isoliert wird,
oder
4-Piperidon der Formel VII, ggf. in Form eines entsprechenden Salzes,
Figure imgb0008
 durch Umsetzung mit einem Carbonsäurederivat der allgemeinen Formel R4-(C=O)-X2, einem Carbonsäureanhydrid der allgemeinen Formel (R4-(C=O))2O oder einer Verbindung der allgemeinen Formel R3-X3, worin R3 die vorstehend genannte Bedeutung mit Ausnahme von Wasserstoff und -(C=O)-R4 hat, der Rest R4 jeweils die vorstehend genannte Bedeutung hat und X2 und X3 jeweils für eine geeignete Austrittsgruppe, vorzugsweise für einen Halogen-Rest, stehen, in eine Verbindung der allgemeinen Formel VIII,
Figure imgb0009
 überführt wird, worin R3 die vorstehend genannte Bedeutung hat, diese ggf. gereinigt und/oder isoliert wird und durch Umsetzung mit wenigstens einer Verbindung der allgemeinen Formel III
Figure imgb0010
 worin R2 die vorstehend genannte Bedeutung hat, in wenigstens eine Verbindung der allgemeinen Formel IX,
Figure imgb0011
 überführt wird, worin R2 und R3 jeweils die vorstehend genannte Bedeutung haben, diese ggf. gereinigt und/oder isoliert wird und durch Umsetzung mit wenigstens einer Verbindung der allgemeinen Formel R1-X1, worin R1 und X1 die vorstehend genannte Bedeutung haben, ggf. in Gegenwart wenigstens einer Base, in wenigstens eine erfindungsgemäße substituierte 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung überführt wird und diese ggf. gereinigt und/oder isoliert wird.A further subject of the present invention is a process for the preparation of the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds according to the invention, according to which a protected piperidin-4-one of the general formula 11
Figure imgb0003
 wherein P is a protective group, by reaction with at least one compound of general formula III,
Figure imgb0004
 in which R 2 has the abovementioned meaning, in at least one compound of the general formula IV,
Figure imgb0005
 wherein P and R 2 have the abovementioned meaning, which is optionally purified and / or optionally isolated, and optionally by reaction with at least one compound of general formula R 1 -X 1 , wherein R 1 has the abovementioned meaning and X 1 is a suitable leaving group, preferably a halogen radical, optionally in the presence of at least one base, in at least one compound of general formula V,
Figure imgb0006
 wherein R 1 , R 2 and P have the abovementioned meaning, is converted, and this optionally purified and / or optionally isolated, and optionally by cleavage of the protective group P in at least one compound of general formula VI,
Figure imgb0007
 if appropriate, this is purified and / or optionally isolated, and if appropriate at least one compound of the general formula IV, V or VI by reaction with a carboxylic acid derivative of the general formula R 4 - (C =O) -X 2 , a Carboxylic anhydride of the general formula (R 4 - (C = O)) 2 O or a compound of the general formula R 3 -X 3 , wherein the radical R 3 has the abovementioned meaning with the exception of hydrogen and - (C = O) -R 4 , R 4 is each as defined above, and X 2 and X 3 are each an appropriate one Leaving group, preferably a halogen radical, is converted into at least one inventive substituted 1,4,8-triazaspiro [4.5] decan-2-one compound, and this compound is optionally purified and / or optionally isolated,
or
4-piperidone of the formula VII, if appropriate in the form of a corresponding salt,
Figure imgb0008
 by reaction with a carboxylic acid derivative of the general formula R 4 - (C = O) -X 2 , a carboxylic anhydride of the general formula (R 4 - (C = O)) 2 O or a compound of the general formula R 3 -X 3 , in which R 3 has the abovementioned meaning with the exception of hydrogen and - (C = O) -R 4 , the radical R 4 in each case has the abovementioned meaning and X 2 and X 3 each represent a suitable leaving group, preferably a halogen radical , in a compound of general formula VIII,
Figure imgb0009
 wherein R 3 has the abovementioned meaning, this is optionally purified and / or isolated and by reaction with at least one compound of general formula III
Figure imgb0010
 wherein R 2 has the abovementioned meaning, in at least one compound of general formula IX,
Figure imgb0011
 wherein R 2 and R 3 are each as defined above, these are optionally purified and / or isolated and by reaction with at least one compound of general formula R 1 -X 1 , wherein R 1 and X 1 are the abovementioned Have meaning, if necessary in the presence of at least one base, in at least one inventive substituted 1,4,8-triazaspiro [4.5] decan-2-one compound is converted and this is optionally purified and / or isolated.

Die N-geschützten Piperidin-4-on-Verbindungen der allgemeinen Formel II sind - ebenso wie ungeschütztes Piperidin-2-on und entsprechende Salze wie beispielsweise dessen Hydrochlorid - käuflich am Markt erhältlich oder können nach üblichen, dem Fachmann bekannten Methoden hergestellt werden. Geeignete Schutzgruppen sind beispielsweise Trifluoracetamid, Methoxycarbonyl, Ethoxycarbonyl, tert-Butoxycarbonyl, Benzyloxycarbonyl, Allyloxycarbonyl oder 9-Fluorenylmethoxycarbonyl,The N-protected piperidin-4-one compounds of general formula II are - as well as unprotected piperidin-2-one and corresponding salts such as its hydrochloride - commercially available on the market or can be prepared by conventional methods known in the art. Suitable protecting groups are, for example, trifluoroacetamide, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, allyloxycarbonyl or 9-fluorenylmethoxycarbonyl,

Die Aminosäureamide der allgemeinen Formel III, die in dem erfindungsgemäßen Verfahren auch in Form ihres entsprechenden Salzes eingesetzt werden können, sind ebenfalls käuflich am Markt erhältlich oder können nach üblichen, dem Fachmann bekannten Methoden hergestellt werden. Die jeweiligen Aminosäureamide können in dem erfindungsgemäßen Verfahren sowohl in enantiomerenreiner Form, d.h. in (S)- oder (R)-Konfiguration, oder in Form eines vorzugsweise racemischen Gemisches mit (S,R)-Konfiguration eingesetzt werden.The amino acid amides of general formula III, which can also be used in the form of their corresponding salt in the process according to the invention, are likewise commercially available or can be prepared by customary methods known to the person skilled in the art. The respective amino acid amides can be used in the inventive method both in enantiomerically pure form, ie in ( S ) - or ( R ) - configuration, or in the form of a preferably racemic mixture with ( S, R ) configuration.

Die Umsetzung von Verbindungen der allgemeinen Formel II mit Verbindungen der allgemeinen Formel III zu N-geschützten, ggf. in 3-Position substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindungen der allgemeinen Formel IV kann unter üblichen, dem Fachmann bekannten Bedingungen erfolgen. Vorzugsweise erfolgt die Umsetzung in einem geeigneten Reaktionsmedium, beispielsweise in einem oder mehreren trockenen organischen Lösungsmitteln. Geeignete Lösungsmittel sind beispielsweise Alkohole wie Ethanol oder chlorierte Kohlenwasserstoffe wie Methylenchlorid oder Chloroform. Die Temperatur während der Vereingung und Umsetzung der Reaktionskomponenten kann über einen weiten Bereich variieren.The reaction of compounds of general formula II with compounds of general formula III to give N-protected, optionally substituted in 3-position, 1,4,8-triaza-spiro [4.5] decan-2-one compounds of general formula IV under customary conditions known to those skilled in the art. Preferably, the reaction is carried out in a suitable reaction medium, for example in one or more dry organic solvents. Suitable solvents are, for example, alcohols such as ethanol or chlorinated hydrocarbons such as methylene chloride or chloroform. The temperature during the annealing and reaction of the reaction components can vary over a wide range.

Die Umsetzung einer N-geschützten, ggf. in 3-Position substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindung der allgemeinen Formel IV mit einer Verbindung der allgemeinen Formel R1-X1 zu Verbindungen der allgemeinen Formel V erfolgt bevorzugt in einem Reaktionsmedium in Gegenwart wenigstens einer organischen Base und/oder in Gegenwart wenigstens einer anorganischen Base unter üblichen, dem Fachmann bekannten Bedingungen. Die Umsetzung kann vorteilhafterweise auch in der Mikrowelle durchgeführt werden.The reaction of an N-protected, optionally substituted in 3-position 1,4,8-triaza-spiro [4.5] decan-2-one compound of general formula IV with a compound of general formula R 1 -X 1 to give compounds The general formula V is preferably carried out in a reaction medium in the presence of at least one organic base and / or in the presence of at least one inorganic base under conventional conditions known in the art. The reaction can be advantageously carried out in the microwave.

Geeignete anorganische Basen sind beispielsweise Metallalkoholate wie Natriummethanolat, Natriumethanolat, Kalium-tert-butylat, Lithium- oder Natriumbasen wie Lithiumdiisopropylamid, Buthyllithium, tert-Butyllithium, Natriummethylat oder Metallhydride wie Kaliumhydrid, Lithiumhydrid, Natriumhydrid. Als geeignete organische Basen kommen beispielsweise Diisopropylethylamin oder Triethylamin in Betracht. Geeignete Reaktionsmedien sind organische Lösungsmittel wie beispielsweise Tetrahydrofuran.Suitable inorganic bases are, for example, metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, lithium or sodium bases such as lithium diisopropylamide, butyllithium, tert-butyllithium, sodium methylate or metal hydrides such as potassium hydride, lithium hydride, sodium hydride. Suitable organic bases include, for example, diisopropylethylamine or triethylamine. Suitable reaction media are organic solvents such as tetrahydrofuran.

Die Abspaltung der Schutzgruppe (P) zur Herstellung von N-ungeschützten, ggf. in 1-und/oder 3-Position substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindungen der allgemeinen Formel VI kann ebenfalls unter üblichen, dem Fachmann bekannten Bedingungen erfolgen, die jeweils in Abhängigkeit von der verwendeten Schutzgruppe variieren. Beispielhaft seien die Abspaltung in Gegenwart einer anorganischen Base, Säure oder Lewis-Säure, wie Kaliumcarbonat, Lithiumhydroxid, Kaliumhydroxid, Schwefelsäure, Bromwasserstoffsäure, Flusssäure, Salzsäure, Bortrifluoridetherat, Bortrichlorid, einer organischen Säure wie Trifluoressigsäure, Trifluormethansulfonsäure, Essigsäure, die Abspaltung in Gegenwart einer organischen Base, wie Morpholin, Triethylamin, Diethylamin, Diisopropylethylamin, Pyridin oder die Hydrierung genannt.The cleavage of the protective group (P) for the preparation of N-unprotected, optionally substituted in 1 and / or 3-position 1,4,8-triaza-spiro [4.5] decan-2-one compounds of general formula VI can also be carried out under customary conditions known in the art, which vary depending on the protecting group used. Examples are the cleavage in the presence of an inorganic base, acid or Lewis acid, such as potassium carbonate, lithium hydroxide, potassium hydroxide, sulfuric acid, hydrobromic acid, hydrofluoric acid, hydrochloric acid, boron trifluoride etherate, boron trichloride, an organic acid such as trifluoroacetic acid, trifluoromethanesulfonic acid, acetic acid, the cleavage in the presence of a organic base such as morpholine, triethylamine, diethylamine, diisopropylethylamine, pyridine or hydrogenation.

Die jeweilige Verbindungen der allgemeinen Formel IV, V oder VI, insbesondere die jeweilige Verbindung der allgemeinen Formel VI, kann anschließend durch Umsetzung mit einem Carbonsäurederivat der allgemeinen Formel R4-(C=O)-X2 oder einem Carbonsäureanhydrid der allgemeinen Formel (R 4-(C=O))2O, worin der Rest R4 jeweils die vorstehend genannte Bedeutung hat und X2 für eine geeignete Austrittsgruppe, vorzugsweise für einen Halogen-Rest, steht vorzugsweise in Gegenwart wenigstens einer organischen Base und/oder wenigstens einer anorganischen Base wie beispielsweise Diisopropylethylamin, Triethylamin, Pyridin oder Diethylamin, ggf. in Gegenwart eines geeigneten Katalysators wie beispielsweise DMAP (Dimethylaminopyridin) unter üblichen, dem Fachmann bekannten Methoden in die jeweilige erfindungsgemäße substituierte 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindung einschließlich entsprechender Stereoisomeren übergeführt werden.The particular compounds of the general formula IV, V or VI, in particular the respective compound of the general formula VI, can then be prepared by reaction with a carboxylic acid derivative of the general formula R 4 - (C = O) -X 2 or a carboxylic anhydride of the general formula (R 4 - (C = O)) 2 O, wherein the radical R 4 has the abovementioned meaning and X 2 is a suitable leaving group, preferably a halogen radical, is preferably in the presence of at least one organic base and / or at least one inorganic base such as diisopropylethylamine, triethylamine, pyridine or diethylamine, optionally in the presence of a suitable catalyst such as DMAP (dimethylaminopyridine) by conventional methods known in the art into the respective substituted 1,4,8-triaza-spiro [4,5] decane according to the invention 2-one compound including corresponding stereoisomers are converted.

Die jeweilige Verbindungen der allgemeinen Formel IV, V oder VI, insbesondere die jeweilige Verbindung der allgemeinen Formel VI, kann anschließend auch durch Umsetzung mit einer Verbindung der allgemeinen Formel R3-X3, worin R3 die vorstehend genannte Bedeutung mit Ausnahme von Wasserstoff und -(C=O)-R4 hat und X2 für eine geeignete Austrittsgruppe, vorzugsweise für einen Halogen-Rest wie beispielsweise Chlor, steht vorzugsweise in Gegenwart wenigstens einer organischen Base und/oder wenigstens einer anorganischen Base wie beispielsweise Diisopropylethylamin, Triethylamin, Pyridin oder Diethylamin nach üblichen, dem Fachmann bekannten Methoden in die jeweilige erfindungsgemäße substituierte 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindung einschließlich entsprechender Stereoisomeren übergeführt werden.The particular compounds of the general formula IV, V or VI, in particular the respective compound of the general formula VI, can then also by reaction with a compound of the general formula R 3 -X 3 , wherein R 3 has the abovementioned meaning with the exception of hydrogen and - (C = O) -R 4 and X 2 is a suitable leaving group, preferably a halogen radical such as chlorine, is preferably in the presence of at least one organic base and / or at least one inorganic base such as diisopropylethylamine, triethylamine, pyridine or diethylamine be converted by customary methods known to those skilled in the respective substituted 1,4,8-triaza-spiro [4.5] decan-2-one compound according to the invention including corresponding stereoisomers.

Die Umsetzung von Verbindungen der allgemeinen Formel IV, V oder VI, insbesondere von Verbindungen der allgemeinen Formel VI, zu einer erfindungsgemäßen substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindung der allgemeinen Formel I erfolgt bevorzugt in einem geeigneten Reaktionsmedium, beispielsweise in einem oder mehreren trockenen organischen Lösungsmitteln. Geeignete Lösungsmittel sind beispielsweise ggf. chlorierte, ggf. aromatische Kohlenwasserstoffe wie Toluol, Methylenchlorid oder Chloroform. Die Temperatur während der Vereingung und Umsetzung der Reaktionskomponenten kann über einen weiten Bereich variieren.The reaction of compounds of the general formula IV, V or VI, in particular of compounds of the general formula VI, to give a substituted 1,4,8-triaza-spiro [4.5] decan-2-one compound of the general formula I according to the invention is preferably carried out in a suitable reaction medium, for example in one or more dry organic solvents. Suitable solvents are, for example, optionally chlorinated, possibly aromatic hydrocarbons such as toluene, methylene chloride or chloroform. The temperature during the annealing and reaction of the reaction components can vary over a wide range.

Die Umsetzung von 4-Piperidon, vorzugsweise in Form des Hydrochlorid-Salzes, mit einem Carbonsäurederivat R4-(C=O)-X2 oder einem Carbonsäurenahydrid (R4-(C=O))2O erfolgt bevorzugt in Gegenwart wenigstens einer organischen Base und/oder in Gegenwart wenigstens einer anorganischen Base. Als geeignete Basen seien Diisopropylethylamin, Triethylamin, Pyridin oder Diethylamin genannt.The reaction of 4-piperidone, preferably in the form of the hydrochloride salt, with a carboxylic acid derivative R 4 - (C =O) -X 2 or a carboxylic acid hydrido (R 4 - (C =O)) 2 O is preferably carried out in the presence of at least one organic base and / or in the presence of at least one inorganic base. Suitable bases include diisopropylethylamine, triethylamine, pyridine or diethylamine.

Die Umsetzung von 4-Piperidon, vorzugsweise in Form des Hydrochlorid-Salzes, mit einer Verbindung R3-X3, worin R3 die vorstehend genannte Bedeutung mit Ausnahme von Wasserstoff und -(C=O)-R4 hat und X3 für eine geeignete Austrittsgruppe, vorzugsweise für einen Halogenrest wie beispielsweise Chlor, steht, erfolgt bevorzugt in Gegenwart wenigstens einer organischen Base und/oder in Gegenwart wenigstens einer anorganischen Base. Als geeignete organische Basen seien Diisopropylethylamin, Triethylamin, Pyridin oder Diethylamin genannt. Als Reaktionsmedium kommen bevorzugt getrockente organische Lösungsmittel wie beispielsweise trochenes Tetrahydrofuran in Betracht.The reaction of 4-piperidone, preferably in the form of the hydrochloride salt, with a compound R 3 -X 3 , wherein R 3 has the abovementioned meaning with the exception of hydrogen and - (C = O) -R 4 and X 3 for a suitable leaving group, preferably a halogen radical such as chlorine, is preferably carried out in the presence of at least one organic base and / or in the presence of at least one inorganic base. As suitable organic bases are Diisopropylethylamine, triethylamine, pyridine or diethylamine called. Preferred reaction media are dried organic solvents such as, for example, trophic tetrahydrofuran.

Die Umsetzung von Verbindungen der allgemeinen Formel VIII mit Verbindungen der allgemeinen Formel III zu in 3-Position substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindungen der allgemeinen Formel IX kann unter üblichen, dem Fachmann bekannten Bedingungen erfolgen. Vorzugsweise erfolgt die Umsetzung in einem geeigneten Reaktionsmedium, beispielsweise in einem oder mehreren trockenen organischen Lösungsmitteln. Geeignete Lösungsmittel sind beispielsweise Alkohole wie Ethanol oder chlorierte Kohlenwasserstoffe wie Methylenchlorid oder Chloroform. Die Temperatur während der Vereingung und Umsetzung der Reaktionskomponenten kann über einen weiten Bereich variieren.The reaction of compounds of general formula VIII with compounds of general formula III to give substituted in 3-position 1,4,8-triaza-spiro [4.5] decane-2-one compounds of general formula IX can under conventional, known in the art Conditions are fulfilled. Preferably, the reaction is carried out in a suitable reaction medium, for example in one or more dry organic solvents. Suitable solvents are, for example, alcohols such as ethanol or chlorinated hydrocarbons such as methylene chloride or chloroform. The temperature during the annealing and reaction of the reaction components can vary over a wide range.

Die Umsetzung einer in 3-Position substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindung der allgemeinen Formel IX mit einer Verbindung der allgemeinen Formel R1-X1 zu einer erfindungsgemäßen 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindung erfolgt bevorzugt in einem Reaktionsmedium in Gegenwart wenigstens einer organischen Base und/oder in Gegenwart wenigstens einer anorganischen Base unter üblichen, dem Fachmann bekannten Bedingungen. Die Umsetzung kann vorteilhafterweise auch in der Mikrowelle durchgeführt werden.
Geeignete anorganische Basen sind beispielsweise Metallalkoholate wie Natriummethanolat, Natriumethanolat, Kalium-tert-butylat, Lithium- oder Natriumbasen wie Lithiumdiisopropylamid, Buthyllithium, tert-Butyllithium, Natriummethylat oder Metallhydride wie Kaliumhydrid, Lithiumhydrid, Natriumhydrid. Als geeignete organische Basen kommen beispielsweise Diisopropylethylamin oder Triethylamin in Betracht. Geeignete Reaktionsmedien sind organische Lösungsmittel wie beispielsweise Tetrahydrofuran.The reaction of a substituted in 3-position 1,4,8-triaza-spiro [4.5] decan-2-one compound of general formula IX with a compound of general formula R 1 -X 1 to a 1,4,8 according to the invention -triaza-spiro [4.5] decan-2-one compound is preferably carried out in a reaction medium in the presence of at least one organic base and / or in the presence of at least one inorganic base under customary conditions known to the person skilled in the art. The reaction can be advantageously carried out in the microwave.
Suitable inorganic bases are, for example, metal alcoholates such as sodium methoxide, sodium ethoxide, potassium tert-butoxide, lithium or sodium bases such as lithium diisopropylamide, butyllithium, tert-butyllithium, sodium methylate or metal hydrides such as potassium hydride, lithium hydride, sodium hydride. Suitable organic bases include, for example, diisopropylethylamine or triethylamine. Suitable reaction media are organic solvents such as tetrahydrofuran.

Die Verbindungen der allgemeinen Formeln R1-X1, R4-(C=O)-X2 und (R4-(C=O))2O, sind jeweils am Markt käuflich erhältlich und/oder können nach üblichen, dem Fachmann bekannten Methoden hergestellt werden. X1 und X2 sind übliche, dem Fachmann bekannte Austrittsgruppen, vorzugsweise Halogen-Reste, besonders bevorzugt Chlor-Reste.The compounds of the general formulas R 1 -X 1 , R 4 - (C = O) -X 2 and (R 4 - (C = O)) 2 O are each commercially available and / or can according to customary, the Professionally known methods are produced. X 1 and X 2 are customary, known in the art leaving groups, preferably halogen radicals, more preferably chlorine radicals.

Die nach den vorstehend beschriebenen Umsetzungen erhaltenen Zwischen- und Endprodukte können jeweils, falls gewünscht und/oder erforderlich, nach üblichen, dem Fachmann bekannten Methoden gereinigt und/oder isoliert werden. Geeignete Reingungsverfahren sind beispielsweise Extraktionsverfahren und chromatographische Verfahren wie Säulenchromatographie oder präparative Chromatographie.The intermediate and end products obtained according to the above-described reactions can each be purified and / or isolated, if desired and / or required, by customary methods known to those skilled in the art. Suitable purification methods are, for example, extraction methods and chromatographic methods, such as column chromatography or preparative chromatography.

Die erfindungsgemäßen substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindungen der vorstehenden allgemeinen Formeln I sowie ggf. jeweils entsprechende Stereoisomere können nach üblichen, dem Fachmann bekannten Verfahren in Form entsprechender Salze, insbesondere in Form entsprechender physiologisch verträglicher Salze erhalten werden, erhalten werden, wobei das erfindungsgemäße Arzneimittel eines oder mehrere Salze einer oder mehrerer dieser Verbindungen aufweisen kann.The substituted 1,4,8-triaza-spiro [4.5] decan-2-one compounds of general formulas I above and optionally corresponding stereoisomers in each case can be prepared by customary methods known to the person skilled in the art in the form of appropriate salts, in particular in the form of corresponding physiologically acceptable salts are obtained, wherein the medicament of the invention may comprise one or more salts of one or more of these compounds.

Die jeweiligen Salze der erfindungsgemäßen substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindungen der vorstehenden allgemeinen Formel I können beispielsweise durch Umsetzung mit einer oder mehreren anorganischen Säuren und/oder einer oder mehreren organischen Säuren erhalten werden. Geeignete Säuren können bevorzugt ausgewählt werden aus der Gruppe bestehend aus Perchlorsäure, Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Methansulfonsäure, Ameisensäure, Essigsäure, Oxalsäure, Bernsteinsäure, Weinsäure, Mandelsäure, Fumarsäure, Milchsäure, Zitronensäure, Glutaminsäure, Sacharinsäure, Cyclohexansulfamidsäure, Aspartam, Monomethylsebacinsäure, 5-Oxo-prolin, Hexan-1-sulfonsäure, Nicotinsäure, 2-Aminobenzoesäure, 3-Aminobenzoesäure oder 4-Aminobenzoesäure, 2,4,6-Trimethylbenzoesäure, α-Liponsäure, Acetylglycin, Hippursäure, Phosphorsäure, Maleinsäure, Malonsäure und Asparaginsäure. Die entsprechenden Hydrochloridsalze werden bevorzugt durch Umsetzung mit Trimethylsilylchlorid in Ethylmethylketon erhalten.The respective salts of the substituted 1,4,8-triaza-spiro [4.5] decan-2-one compounds of the general formula I according to the invention can be obtained, for example, by reaction with one or more inorganic acids and / or one or more organic acids , Suitable acids may preferably be selected from the group consisting of perchloric, hydrochloric, hydrobromic, sulfuric, methanesulfonic, formic, acetic, oxalic, succinic, tartaric, mandelic, fumaric, lactic, citric, glutamic, succinic, cyclohexanesulfamic, aspartame, monomethylsebacic, 5 Oxo-proline, hexane-1-sulfonic acid, nicotinic acid, 2-aminobenzoic acid, 3-aminobenzoic acid or 4-aminobenzoic acid, 2,4,6-trimethylbenzoic acid, α-lipoic acid, acetylglycine, hippuric acid, phosphoric acid, maleic acid, malonic acid and aspartic acid. The corresponding hydrochloride salts are preferably obtained by reaction with trimethylsilyl chloride in ethyl methyl ketone.

Die erfindungsgemäßen substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindungen der vorstehenden allgemeinen Formel I sowie ggf. entsprechende Stereoisomere und jeweils deren physiologisch verträgliche Salze können auch nach üblichen, dem Fachmann bekannten Verfahren in Form ihrer Solvate, insbesondere in Form ihrer Hydrate erhalten werden.The substituted 1,4,8-triaza-spiro [4.5] decan-2-one compounds of the general formula I above and optionally corresponding stereoisomers and in each case their physiologically acceptable salts can also be prepared by conventional methods known to the person skilled in the art in the form of theirs Solvates, especially in the form of their hydrates can be obtained.

Sofern die erfindungsgemäßen substituierten 1,4,8-triaza-spiro[4.5]decan-2-on-Verbindungen der vorstehenden allgemeinen Formel I nach ihrer Herstellung in Form einer Mischung ihrer Stereoisomeren, vorzugsweise in Form ihrer Racemate oder anderer Mischungen ihrer verschiedenen Enantiomeren und/oder Diastereomeren erhalten werden, können diese nach üblichen, dem Fachmann bekannten Verfahren getrennt und ggf. isoliert werden. Beispielhaft seien chromatographische Trennverfahren, insbesondere Flüssigkeits-chromatographie-Verfahren unter Normaldruck oder unter erhöhtem Druck, bevorzugt MPLC- und HPLC-Verfahren, sowie Verfahren der fraktionierten Kristallisation genannt. Dabei können insbesondere einzelne Enantiomere, z.B. mittels HPLC an chiraler Phase oder mittels Kristallisation mit chiralen Säuren, etwa (+)-Weinsäure, (-)-Weinsäure oder (+)-10-Camphersulfonsäure, gebildete diastereomere Salze voneinander getrennt werden.If the substituted 1,4,8-triaza-spiro [4.5] decan-2-one compounds of the general formula I according to the invention after their preparation in the form of a mixture of their stereoisomers, preferably in the form of their racemates or other mixtures of their different enantiomers and / or diastereomers are obtained, these can be separated by conventional methods known in the art and optionally isolated. Examples which may be mentioned are chromatographic separation processes, in particular liquid chromatography processes under atmospheric pressure or under elevated pressure, preferably MPLC and HPLC processes, and also fractional crystallization processes. In particular, single enantiomers, e.g. be separated by chiral HPLC or by crystallization with chiral acids, such as (+) - tartaric acid, (-) - tartaric acid or (+) - 10-camphorsulfonic acid formed diastereomeric salts.

Es wurde überraschenderweise gefunden, daß die 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I sich nicht nur zur Regulation, vorzugsweise zur Inhibierung, der Noradrenalin-Wiederaufnahme und/oder zur Regulation, vorzugsweise zur Inhibierung, der 5-Hydroxy-Tryptophan-Wiederaufnahme eignen, sondern darüber hinaus auch eine hohe Affinität für Opioid-Rezeptoren, insbesondere für µ-Opioid-Rezeptoren und für Batrachotoxin-(BTX)-Rezeptoren aufweisen und sich daher insbesondere als pharmazeutische Wirkstoffe in Arzneimitteln zur Prophylaxe und/oder Behandlung von mit diesen Rezeptoren bzw. Prozessen in Verbindung stehenden Erkrankungen eignen.It has surprisingly been found that the 1,4,8-triazaspiro [4.5] decan-2-one compounds of the above-indicated general formula I are not only useful for regulating, preferably for inhibiting, norepinephrine reuptake and / or for regulating, preferably for inhibition, the 5-hydroxy-tryptophan reuptake are suitable, but also have a high affinity for opioid receptors, in particular for μ-opioid receptors and for batrachotoxin (BTX) receptors and therefore in particular as pharmaceutical agents in medicaments for the prophylaxis and / or treatment of disorders associated with these receptors or processes.

Die 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I und ggf. entsprechende Stereoisomere sowie jeweils die entsprechenden Salze und Solvate sind toxikologisch unbedenklich und eignen sich daher als pharmazeutische Wirkstoffe in Arzneimitteln.The 1,4,8-triazaspiro [4.5] decan-2-one compounds of the above-mentioned general formula I and optionally corresponding stereoisomers and in each case the corresponding salts and solvates are toxicologically harmless and are therefore suitable as pharmaceutical active ingredients in medicaments.

Ein weiterer Gegenstand der vorliegenden Erfindung ist daher ein Arzneimittel enthaltend wenigstens eine erfindungsgemäße 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der vorstehend angegebenen allgemeinen Formel I, ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates, sowie ggf. wenigstens einen pharmazeutisch verträglichen Hilfsstoff.Another object of the present invention is therefore a medicament containing at least one inventive 1,4,8-triazaspiro [4.5] decan-2-one compound of the above general formula I, optionally in the form of one of its pure stereoisomers, especially enantiomers or Diastereomers, their racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate, and optionally at least one pharmaceutically compatible excipient.

Bevorzugt sind Arzneimittel, die wenigstens eine 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der vorstehend angegebenen allgemeinen Formel I mit Ausnahme der Verbindungen gemäß A) und/oder mit Ausnahme der Verbindungen gemäß B) enthalten, ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates, sowie ggf. wenigstens einen pharmazeutisch verträglichen Hilfsstoff enthalten.Preference is given to medicaments which comprise at least one 1,4,8-triazaspiro [4.5] decan-2-one compound of the abovementioned general formula I with the exception of the compounds according to A) and / or with the exception of the compounds according to B), if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in Form of a corresponding solvate, and optionally contain at least one pharmaceutically acceptable excipient.

Vorzugsweise eignet sich das erfindungsgemäße Arzneimittel zur Regulation, insbesondere zur Hemmung, der Noradrenalin-Wiederaufnahme (Noradrenalin-Uptake), zur Regulation, insbesondere zur Hemmung, der 5-Hydroxy-Tryptophan-Wiederaufnahme (5-HT-Uptake), zur Opioid-Rezeptor-Regulation, insbesondere zur µ-Opioid-Rezeptor-Regulation und/oder zur Batrachotoxin-(BTX)-Rezeptor-Regulation.The medicament according to the invention is preferably suitable for the regulation, in particular for the inhibition, of norepinephrine reuptake (norepinephrine uptake), for the regulation, in particular for the inhibition, of 5-hydroxy-tryptophan reuptake (5-HT-uptake), for the opioid receptor -Regulation, in particular for μ-opioid receptor regulation and / or for batrachotoxin (BTX) receptor regulation.

Ebenfalls bevorzugt eignet sich das erfindungsgemäße Arzneimittel zur Prophylaxe und/oder Behandlung von Störungen der Nahrungsmittelaufnahme, vorzugsweise ausgewählt aus der Gruppe bestehend aus Bulimie, Anorexie, Fettsucht und Kachexie, besonders bevorzugt zur Prophylaxe und/oder Behandlung von Fettsucht.The medicament according to the invention is likewise preferably suitable for the prophylaxis and / or treatment of disorders of food intake, preferably selected from the group consisting of bulimia, anorexia, obesity and cachexia, particularly preferably for the prophylaxis and / or treatment of obesity.

Ebenfalls bevorzugt eignet sich das erfindungsgemäße Arzneimittel zur Prophylaxe und/oder Behandlung von Schmerzen, vorzugsweise zur Behandlung und/oder Prophylaxe von akuten Schmerzen, chronischen Schmerzen, neuropathischen Schmerzen und/oder Clusterkopfschmerzen, oder zur Prophylaxe und/oder Behandlung von Depressionen.The medicament according to the invention is likewise preferably suitable for the prophylaxis and / or treatment of pain, preferably for the treatment and / or prophylaxis of acute pain, chronic pain, neuropathic pain and / or cluster headache, or for the prophylaxis and / or treatment of depression.

Besonders bevorzugt eignet sich das erfindungsgemäße Arzneimittel zur kombinierten Prophylaxe und/oder Behandlung von Depressionen und Schmerzen, vorzugsweise zur kombinierten Behandlung von Depressionen und Schmerzen ausgewählt aus der Gruppe bestehend aus akuten Schmerzen, chronischen Schmerzen, neuropathischen Schmerzen und Clusterkopfschmerzen.The medicament according to the invention is particularly preferably suitable for the combined prophylaxis and / or treatment of depression and pain, preferably for the combined treatment of depression and pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and cluster headache.

Weiterhin bevorzugt eignet sich das erfindungsgemäße Arzneimittel zur Prophylaxe und/oder Behandlung von Akohol- und/oder Drogen- und/oder Medikamentenmißbrauch, zur Prophylaxe und/oder Behandlung von Akohol- und/oder Drogen- und/oder Medikamentenabhängigkeit, zur Prophylaxe und/oder Behandlung von Entzündungen, zur Prophylaxe und/oder Behandlung von Antriebslosigkeit, zur Prophylaxe und/oder Behandlung von Katalepsie, zur Vigilanzsteigerung, zur Libidosteigerung, zur Anxiolyse, zur Prophylaxe und/oder Behandlung von neurodegenerativen Erkrankungen, vorzugsweise einer oder mehrerer neurodegenerativer Erkrankungen ausgewählt aus der Gruppe bestehend aus Morbus Parkinson, Morbus Huntington, Morbus Alzheimer und Multipler Sklerose, zur Prophylaxe und/oder Behandlung von Ischämien und/oder zur Lokalanästhesie.Further preferably, the medicament of the invention is suitable for the prophylaxis and / or treatment of alcohol and / or drug and / or drug abuse, for the prophylaxis and / or treatment of alcohol and / or drug and / or drug dependence, for prophylaxis and / or Treatment of inflammation, for the prophylaxis and / or treatment of listlessness, for the prophylaxis and / or treatment of catalepsy, for vigilance enhancement, for libido enhancement, for anxiolysis, for the prophylaxis and / or treatment of neurodegenerative diseases, preferably one or more neurodegenerative diseases selected from Group consisting of Parkinson's disease, Huntington's disease, Alzheimer's disease and multiple sclerosis, for the prophylaxis and / or treatment of ischaemias and / or local anesthetics.

Ein weiterer Gegenstand der vorliegenden Erfindung ist die Verwendung wenigstens einer erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der allgemeinen Formel I, ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates, zur Herstellung eines Arzneimittels zur Regulation der Noradrenalin-Wiederaufnahme (Noradrenalin-Uptake), vorzugsweise zur Hemmung der Noradrenalin-Wiederaufnahme (Noradrenalin-Uptake), zur Regulation der 5-Hydroxy-Tryptophan-Wiederaufnahme (5-HT-Uptake), vorzugsweise zur Hemmung der 5-Hydroxy-Tryptophan-Wiederaufnahme (5-HT-Uptake), zur Opioid-Rezeptor-Regulation, vorzugsweise zur µ-Opioid-Rezeptor-Regulation und/oder zur zur Batrachotoxin-(BTX)-Rezeptor-Regulation.Another object of the present invention is the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of general formula I according to the invention, optionally in the form of one of its pure stereoisomers, especially enantiomers or diastereomers, of their Racemates or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate, for the preparation of a medicament for the regulation of noradrenaline Recovery (norepinephrine uptake), preferably for the inhibition of norepinephrine reuptake (norepinephrine uptake), for the regulation of 5-hydroxy-tryptophan reuptake (5-HT-uptake), preferably for the inhibition of 5-hydroxy-tryptophan reuptake (5-HT-uptake), for opioid receptor regulation, preferably for μ-opioid receptor regulation and / or for batrachotoxin (BTX) receptor regulation.

Bevorzugt ist die Verwendung wenigstens einer erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der allgemeinen Formel I, ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates zur Herstellung eines Arzneimittels zur Prophylaxe und/oder Behandlung von Störungen der Nahrungsmittelaufnahme, vorzugsweise ausgewählt aus der Gruppe bestehend aus Bulimie, Anorexie, Fettsucht und Kachexie, besonders bevorzugt Fettsucht.Preference is given to the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention, if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form of a Mixture of stereoisomers, in particular of the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate for the preparation of a medicament for the prophylaxis and / or treatment of disorders of food intake, preferably selected from the group consisting of bulimia, anorexia, obesity and cachexia, more preferably obesity.

Bevorzugt ist die Verwendung wenigstens einer erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der allgemeinen Formel I, ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates zur Herstellung eines Arzneimittels zur Prophylaxe und/oder Behandlung von Schmerzen, vorzugsweise von akuten Schmerzen, chronischen Schmerzen, neuropathischen Schmerzen und/oder Clusterkopfschmerzen.Preference is given to the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention, if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form of a Mixture of stereoisomers, in particular of the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate for the preparation of a medicament for the prophylaxis and / or treatment of pain, preferably of acute pain, chronic pain, neuropathic pain and / or cluster headache.

Bevorzugt ist ferner die Verwendung wenigstens einer erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der allgemeinen Formel I, ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates zur Herstellung eines Arzneimittels zur Prophylaxe und/oder Behandlung von Depressionen.Also preferred is the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention, if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate for the preparation of a medicament for the prophylaxis and / or treatment of depression.

Bevorzugt ist weiterhin die Verwendung wenigstens einer erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der allgemeinen Formel I, ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates zur Herstellung eines Arzneimittels zur kombinierten Prophylaxe und/oder Behandlung von Depressionen und Schmerzen, vorzugsweise zur kombinierten Behandlung von Depressionen und Schmerzen ausgewählt aus der Gruppe bestehend aus akuten Schmerzen, chronischen Schmerzen, neuropathischen Schmerzen und Clusterkopfschmerzen.Also preferred is the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention, if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form a mixture of stereoisomers, in particular of the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate for the preparation of a medicament for the combined prophylaxis and / or treatment of depression and Pain, preferably for the combined treatment of depression and pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and cluster headache.

Bevorzugt ist auch die Verwendung wenigstens einer erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der allgemeinen Formel I, ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates, zur Herstellung eines Arzneimittels zur Prophylaxe und/oder Behandlung von Akohol- und/oder Drogen- und/oder Medikamentenmißbrauch, zur Prophylaxe und/oder Behandlung von Akohol- und/oder Drogen- und/oder Medikamentenabhängigkeit, zur Prophylaxe und/oder Behandlung von Entzündungen, zur Prophylaxe und/oder Behandlung von Antriebslosigkeit, zur Prophylaxe und/oder, zur Prophylaxe und/oder Behandlung von Katalepsie, zur Vigilanzsteigerung, zur Libidosteigerung, zur Anxiolyse, zur Prophylaxe und/oder Behandlung von neurodegenerativen Erkrankungen, vorzugsweise einer oder mehrerer neurodegenerativer Erkrankungen ausgewählt aus der Gruppe bestehend aus Morbus Parkinson, Morbus Huntington, Morbus Alzheimer und Multipler Sklerose, zur Prophylaxe und/oder Behandlung von Ischämien und/oder zur Lokalanästhesie.Also preferred is the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention, if appropriate in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form a mixture of stereoisomers, in particular of the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate, for the preparation of a medicament for the prophylaxis and / or treatment of alcohol and / or drug and / or drug abuse, for the prophylaxis and / or treatment of alcohol and / or drug and / or drug dependence, for the prophylaxis and / or treatment of inflammation, for the prophylaxis and / or treatment of listlessness, for prophylaxis and / or, for the prophylaxis and / or treatment of catalepsy, to increase vigilance, to libido Anxiolysis, for the prophylaxis and / or treatment of neurodegenerative diseases, preferably one or more neurodegenerative diseases selected from the group consisting of Parkinson's disease, Huntington's disease, Alzheimer's disease and multiple sclerosis, for the prophylaxis and / or treatment of ischaemias and / or local anesthetics.

Besonders bevorzugt kann auch jeweils die Verwendung wenigstens einer erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung der allgemeinen Formel I mit Ausnahme der Verbindungen gemäß A) und/oder mit Ausnahme der Verbindungen gemäß B), jeweils ggf. in Form eines ihrer reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form einer Mischung von Stereoisomeren, insbesondere der Enantiomeren und/oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder jeweils in Form eines entsprechenden Salzes, vorzugsweise Hydrochlorids, oder jeweils in Form eines entsprechenden Solvates, zur Herstellung eines Arzneimittels zur Prophylaxe und/oder Behandlung der vorstehend genannten Krankheiten bzw. Störungen erfolgen.Particular preference may also be given in each case to the use of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound of the general formula I according to the invention with the exception of the compounds according to A) and / or with the exception of the compounds according to B), in each case optionally in the form of one of its pure stereoisomers, in particular enantiomers or diastereomers, of its racemate or in the form of a mixture of stereoisomers, in particular the enantiomers and / or diastereomers, in any mixing ratio, or in each case in the form of a corresponding salt, preferably hydrochloride, or in each case in the form of a corresponding solvate, for the preparation of a medicament for the prophylaxis and / or treatment of the abovementioned diseases or disorders.

Das erfindungsgemäße Arzneimittel eignet sich zur Verabreichung an Erwachsene und Kinder einschließlich Kleinkindern und Säuglingen.The pharmaceutical composition of the invention is suitable for administration to adults and children, including infants and babies.

Das erfindungsgemäße Arzneimittel kann als flüssige, halbfeste oder feste Arzneiform, beispielsweise in Form von Injektionslösungen, Tropfen, Säften, Sirupen, Sprays, Suspensionen, Tabletten, Patches, Kapseln, Pflastern, Zäpfchen, Salben, Cremes, Lotionen, Gelen, Emulsionen, Aerosolen oder in multipartikulärer Form, beispielsweise in Form von Pellets oder Granulaten, ggf. zu Tabletten verpreßt, in Kapseln abgefüllt oder in einer Flüssigkeit suspendiert, vorliegen und als solche auch verabreicht werden.The medicament according to the invention can be used as a liquid, semisolid or solid dosage form, for example in the form of injection solutions, drops, juices, syrups, sprays, suspensions, tablets, patches, capsules, patches, suppositories, ointments, creams, lotions, gels, emulsions, aerosols or in multiparticulate form, for example in the form of pellets or granules, optionally compressed into tablets, filled into capsules or suspended in a liquid, are present and as such also administered.

Neben einer oder mehreren der in dem erfindungsgemäßen Arzneimittel zum Einsatz kommenden substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehenden allgemeinen Formel I, ggf. in Form ihres reinen Stereoisomeren, insbesondere Enantiomeren oder Diastereomeren, ihres Racemates oder in Form von Mischungen der Stereoisomeren, insbesondere der Enantiomeren oder Diastereomeren, in einem beliebigen Mischungsverhältnis, oder ggf. in Form eines entsprechenden Salzes oder jeweils in Form eines entsprechendes Solvates, enthält das erfindungsgemäße Arzneimittel üblicherweise weitere physiologisch verträgliche pharmazeutische Hilfsstoffe, die bevorzugt ausgewählt werden können aus der Gruppe bestehend aus Trägermaterialien, Füllstoffen, Lösungsmitteln, Verdünnungsmitteln, oberflächenaktiven Stoffen, Farbstoffen, Konservierungsstoffen, SprengmitteIn, Gleitmitteln, Schmiermitteln, Aromen und Bindemitteln.Besides one or more of the substituted 1,4,8-triazaspiro [4,5] decan-2-one compounds of the general formula I above, if appropriate in the form of their pure stereoisomers, in particular enantiomers or diastereomers, of the abovementioned pharmaceutical compositions Racemates or in the form of mixtures of stereoisomers, in particular the enantiomers or diastereomers, in any mixing ratio, or optionally in the form of a corresponding salt or in each case in the form of a corresponding solvate the medicament of the invention usually further physiologically acceptable pharmaceutical excipients, which may be preferably selected from the group consisting of excipients, fillers, solvents, diluents, surfactants, dyes, preservatives, blasting agents, lubricants, lubricants, flavors and binders.

Die Auswahl der physiologisch verträglichen Hilfsstoffe sowie die einzusetzenden Mengen derselben hängt davon ab, ob das Arzneimittel oral, subkutan, parenteral, intravenös, intraperitoneal, intradermal, intramuskulär, intranasal, buccal, rectal oder örtlich, zum Beispiel auf Infektionen an der Haut, der Schleimhäute und an den Augen, appliziert werden soll. Für die orale Applikation eignen sich bevorzugt Zubereitungen in Form von Tabletten, Dragees, Kapseln, Granulaten, Pellets, Tropfen, Säften und Sirupen, für die parenterale, topische und inhalative Applikation Lösungen, Suspensionen, leicht rekonstituierbare Trockenzubereitungen sowie Sprays.The choice of the physiologically acceptable excipients and the amounts to be used depend on whether the drug is oral, subcutaneous, parenteral, intravenous, intraperitoneal, intradermal, intramuscular, intranasal, buccal, rectal or topical, for example, skin infections, mucous membranes and on the eyes, to be applied. Preparations in the form of tablets, dragees, capsules, granules, pellets, drops, juices and syrups are preferred for oral administration, solutions, suspensions, readily reconstitutable dry preparations and sprays for parenteral, topical and inhalative administration.

Die in dem erfindungsgemäßen Arzneimittel zum Einsatz kommenden substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen in einem Depot in gelöster Form oder in einem Pflaster, gegebenenfalls unter Zusatz von die Hautpenetration fördernden Mitteln, sind geeignete perkutane Applikationszubereitungen.
Oral oder perkutan anwendbare Zubereitungsformen können die jeweiligen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen auch verzögert freisetzen.The substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds used in the medicament according to the invention in a depot in dissolved form or in a plaster, optionally with the addition of skin penetration-promoting agents, are suitable percutaneous administration preparations ,
Orally or percutaneously applicable formulations may also release the respective substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds with a delay.

Die Herstellung der erfindungsgemäßen Arzneimittel erfolgt mittels üblichen, aus dem Stande der Technik wohl bekannten Mitteln, Vorrichtungen, Methoden und Verfahren, wie sie beispielsweise in "Remington's Pharmaceutical Sciences", Herausgeber A.R. Gennaro, 17. Auflage, Mack Publishing Company, Easton, Pa, 1985, insbesondere in Teil 8, Kapitel 76 bis 93 beschrieben sind. Die entsprechende Beschreibung wird hiermit als Referenz eingeführt und gilt als Teil der Offenbarung.The pharmaceutical compositions of the invention are prepared by conventional means, devices, methods and procedures well known in the art, as described, for example, in "Remington's Pharmaceutical Sciences", published by AR Gennaro, 17th Edition, Mack Publishing Company, Easton, Pa. 1985, in particular in Part 8, Chapters 76 to 93 are described. The corresponding description is hereby incorporated by reference and is considered part of the disclosure.

Die an den Patienten zu verabreichende Menge der jeweiligen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung kann variieren und ist beispielsweise abhängig vom Gewicht oder Alter des Patienten sowie von der Applikationsart, der Indikation und dem Schweregrad der Erkrankung. Üblicherweise werden 0,005 bis 50 mg/kg, vorzugsweise 0,05 bis 50 mg/kg Körpergewicht des Patienten wenigstens einer erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindung appliziert.The amount of the respective substituted 1,4,8-triazaspiro [4.5] decan-2-one compound to be administered to the patient may vary and depends, for example, on the weight or age of the patient as well as on the mode of administration, the indication and the severity of the disease Illness. Usually, 0.005 to 50 mg / kg, preferably 0.05 to 50 mg / kg of body weight of the patient of at least one substituted 1,4,8-triazaspiro [4.5] decan-2-one compound according to the invention are administered.

Pharmakologischen Methoden:Pharmacological methods: I. Analgesieprüfung im Writhing-Test an der MausI. Analgesia test in the writhing test on the mouse

Die Untersuchung auf analgetische Wirksamkeit wird im Phenylchinon-induzierten Writhing an der Maus (modifiziert nach I.C. Hendershot und J. Forsaith (1959) J. Pharmacol. Exp. Ther. 125, 237-240 ) durchgeführt. Die entsprechende Beschreibung wird hiermit als Referenz eingeführt und gilt als Teil der vorliegenden Offenbarung.The assay for analgesic efficacy is described in phenyl-quinone-induced writhing in the mouse (modified after IC Hendershot and J. Forsaith (1959) J. Pharmacol. Exp. Ther. 125, 237-240 ) carried out. The corresponding description is hereby incorporated by reference and is considered part of the present disclosure.

Dazu werden männliche NMRI-Mäuse im Gewicht von 25 bis 30 g verwendet. Gruppen von 10 Tieren pro Substanzdosis erhalten 10 Minuten nach intravenöser Gabe der Prüfsubstanzen 0,3 ml/Maus einer 0,02%igen wäßrigen Lösung von Phenylchinon (Phenylbenzochinon, Fa. Sigma, Deisenhofen; Herstellung der Lösung unter Zusatz von 5 % Äthanol und Aufbewahrung im Wasserbad bei 45°C) intraperitoneal appliziert. Die Tiere werden einzeln in Beobachtungskäfige gesetzt. Mittels eines Drucktastenzähler wird die Anzahl der schmerzinduzierten Streckbewegungen (sogenannte Writhingreaktionen = Durchdrücken des Körpers mit Abstrecken der Hinterextremitäten) 5 bis 20 Minuten nach der Phenylchinon-Gabe ausgezählt. Als Kontrolle werden Tiere mitgeführt, die nur physiologische Kochsalzlösung erhalten. Alle Substanzen werden in der Standarddosierung von 10 mg/kg getestet. Die prozentuale Hemmung (%Hemmung) der Writhingreaktion durch eine Substanz wird nach folgender Formel berechnet: % H ⁢ e ⁢ m ⁢ m ⁢ u ⁢ n ⁢ g = 100 − W ⁢ r ⁢ i ⁢ t ⁢ h ⁢ i ⁢ n ⁢ g ⁢ r ⁢ e ⁢ a ⁢ k ⁢ t ⁢ i ⁢ o ⁢ n ⁢ e ⁢ n d ⁢ e ⁢ r b ⁢ e ⁢ h ⁢ a ⁢ n ⁢ d ⁢ e ⁢ l ⁢ t ⁢ e ⁢ n T ⁢ i ⁢ e ⁢ r ⁢ e * 100 W ⁢ r ⁢ i ⁢ t ⁢ h ⁢ i ⁢ n ⁢ g ⁢ r ⁢ e ⁢ a ⁢ k ⁢ t ⁢ i ⁢ o ⁢ n ⁢ e ⁢ n d ⁢ e ⁢ r K ⁢ o ⁢ n ⁢ t ⁢ r ⁢ o ⁢ l ⁢ l ⁢ t ⁢ i ⁢ e ⁢ r ⁢ e

Figure imgb0012
For this purpose male NMRI mice weighing 25 to 30 g are used. 10 minutes after intravenous administration of the test substances, groups of 10 animals per substance dose receive 0.3 ml / mouse of a 0.02% strength aqueous solution of phenylquinone (phenylbenzoquinone, Sigma, Deisenhofen, preparation of the solution with addition of 5% ethanol and storage in a water bath at 45 ° C) intraperitoneally. The animals are placed individually in observation cages. By means of a push-button counter, the number of pain-induced stretching movements (so-called writhing reactions = pushing through of the body with hindlegging) is counted 5 to 20 minutes after the administration of phenylquinone. As a control animals are carried, which receive only physiological saline. All substances are tested in the standard dosage of 10 mg / kg. The percentage inhibition (% inhibition) of the writhing reaction by a substance is calculated according to the following formula: % H ⁢ e ⁢ m ⁢ m ⁢ u ⁢ n ⁢ G = 100 - W ⁢ r ⁢ i ⁢ t ⁢ H ⁢ i ⁢ n ⁢ G ⁢ r ⁢ e ⁢ a ⁢ k ⁢ t ⁢ i ⁢ O ⁢ n ⁢ e ⁢ n d ⁢ e ⁢ r b ⁢ e ⁢ H ⁢ a ⁢ n ⁢ d ⁢ e ⁢ l ⁢ t ⁢ e ⁢ n T ⁢ i ⁢ e ⁢ r ⁢ e * 100 W ⁢ r ⁢ i ⁢ t ⁢ H ⁢ i ⁢ n ⁢ G ⁢ r ⁢ e ⁢ a ⁢ k ⁢ t ⁢ i ⁢ O ⁢ n ⁢ e ⁢ n d ⁢ e ⁢ r K ⁢ O ⁢ n ⁢ t ⁢ r ⁢ O ⁢ l ⁢ l ⁢ t ⁢ i ⁢ e ⁢ r ⁢ e
Figure imgb0012

Für einige Substanzen wird aus der dosisabhängigen Abnahme der Writhingreaktionen im Vergleich zu parallel untersuchten Phenylchinon-Kontrollgruppen mittels Regressionsanalyse (Auswerteprogramm Martens EDV Service, Eckental) die ED50-Werte mit 95 % Vertrauensbereich der Writhingreaktion berechnet.For some substances, the ED 50 values with 95% confidence interval of the writhing reaction are calculated from the dose-dependent decrease of the writhing reactions in comparison to parallel examined phenylquinone control groups by regression analysis (evaluation program Martens EDV Service, Eckental).

II. Methode zur Bestimmung der Affinität zum humanen µ-Opioidrezeptor: II. Method for Determining the Affinity for the Human μ Opioid Receptor

Die Rezeptoraffinität zum humanen µ-Opioidrezeptor wird in einem homogenen Ansatz in Mikrotiterplatten bestimmt. Hierzu werden Verdünnungsreihen der zu prüfenden Substanzen mit einer Rezeptormembranpräparation (15-40 µg Protein /250 µl Inkubationsansatz) von CHO-K1-Zellen, welche den humanen µ-Opioidrezeptor exprimieren (RB-HOM-Rezeptormembran-Präparation von der Firma NEN, Zaventem, Belgien) in Gegenwart von 1 nmol/I des radioaktiven Liganden [3H]-Naloxon (NET 719, Firma NEN, Zaventem, Belgien) sowie von 1 mg WGA-SPA-Beads (Wheat germ agglutinin SPA Beads der Firma Amersham/Pharmacia, Freiburg, Deutschland) in einem Gesamtvolumen von 250 µl für 90 Minuten bei Raumtemperatur inkubiert. Als Inkubationspuffer wird 50 mmol/l Tris-HCl supplementiert mit 0,05 % (Gewicht/Volumen) Natriumazid und mit 0,06 % (Gewicht/Volumen) bovinem Serumalbumin verwendet. Zur Bestimmung der unspezifischen Bindung wird zusätzlich 25 µmol/I Naloxon zugegeben. Nach Beendigung der neunzigminütigen Inkubationszeit werden die Mikrotiterplatten für 20 Minuten bei 1000 g abzentrifugiert und die Radioaktivität in einem β-Counter (Microbeta-Trilux, Firma PerkinEImer Wallac, Freiburg, Deutschland) vermessen. Es wird die prozentuale Verdrängung des radioaktiven Liganden aus seiner Bindung zum humanen µ-Opioidrezeptor bei einer Konzentration der Prüfsubstanzen von 1 µmol/l bestimmt und als Prozent Hemmung der spezifischen Bindung angegeben.The receptor affinity for the human μ-opioid receptor is determined in a homogeneous batch in microtiter plates. For this purpose, dilution series of the substances to be tested are prepared with a receptor membrane preparation (15-40 μg protein / 250 μl incubation mixture) of CHO-K1 cells which express the human μ-opioid receptor (RB-HOM receptor membrane preparation from NEN, Zaventem, Belgium) in the presence of 1 nmol / l of the radioactive ligand [ 3 H] -naloxone (NET 719, NEN, Zaventem, Belgium) and 1 mg of WGA-SPA beads (Wheat germ agglutinin SPA beads from Amersham / Pharmacia, Freiburg, Germany) in a total volume of 250 μl for 90 minutes at room temperature. Incubation buffer is 50 mmol / l Tris-HCl supplemented with 0.05% (w / v) sodium azide and 0.06% (w / v) bovine serum albumin. To determine the unspecific binding, an additional 25 μmol / I naloxone is added. After the ninety-minute incubation period, the microtiter plates are centrifuged for 20 minutes at 1000 g and the radioactivity in a β-counter (Microbeta-Trilux, PerkinEImer Wallac, Freiburg, Germany) measured. The percentage displacement of the radioactive ligand from its binding to the human μ-opioid receptor at a concentration of the test substances of 1 μmol / l is determined and stated as percent inhibition of the specific binding.

Ausgehend von der prozentualen Verdrängung durch unterschiedliche Konzentrationen der Prüfsubstanzen werden IC50 Hemmkonzentrationen berechnet, die eine 50-prozentige Verdrängung des radioaktiven Liganden bewirken. Durch Umrechnung mittels der Cheng-Prusoff-Beziehung können die Ki-Werte für die Prüfsubstanzen erhalten werden, wie in der Veröffentlichung von Y. Cheng, W.H. Prusoff, 1973, Biochem. Pharmacol., 22, Seiten 3099-3108 beschrieben. Die entsprechende Beschreibung wird hiermit als Referenz eingeführt und gilt als Teil der vorliegenden Offenbarung.Based on the percentage displacement by different concentrations of the test substances IC 50 inhibitory concentrations are calculated, which cause a 50 percent displacement of the radioactive ligand. By conversion using the Cheng-Prusoff relationship, the Ki values for the test substances can be obtained, as in the publication of Y. Cheng, WH Prusoff, 1973, Biochem. Pharmacol., 22, pp. 3099-3108 described. The corresponding description is hereby incorporated by reference and is considered part of the present disclosure.

III. Methode zur Bestimmung der Noradrenalin- und der 5HT-Uptake-Inhibierung:III. Method for Determining Noradrenaline and 5HT Uptake Inhibition:

Für in vitro Studien werden Synaptosomen aus Rattenhimarealen frisch isoliert, wie in der Veröffentlichung " The isolation of nerve endings from brain" von E.G. Gray und V.P. Whittaker, J. Anatomy 96, Seiten 79-88, 1962 , beschrieben. Die entsprechende Literaturbeschreibung wird hiermit als Referenz eingeführt und gilt als Teil der Offenbarung.For in vitro studies, rat mammalian synaptosomes are freshly isolated as described in the publication " The isolation of nerve endings from brain "by EG Gray and VP Whittaker, J. Anatomy 96, pages 79-88, 1962 , described. The corresponding literature description is hereby incorporated by reference and is considered part of the disclosure.

Das Gewebe (Hypothalamus für die Bestimmung der Noradrenalin-Uptake-Inhibierung und Mark und Pons für die Bestimmung der 5HT-Uptake-Inhibierung) wird in eisgekühlter 0,32 M Sucrose (100 mg Gewebe / 1 mL) in einem Glas-Homogenisierer mit Teflonstößel homogenisiert, indem fünf volle Auf- und Abschläge bei 840 Umdrehungen /Minute benutzt werden.The tissue (hypothalamus for the determination of norepinephrine uptake inhibition and mark and pons for the determination of 5HT-uptake inhibition) is suspended in ice-cooled 0.32 M sucrose (100 mg tissue / 1 mL) in a glass homogenizer with Teflon pestle Homogenized using five full up and downs at 840 rpm.

Das Homogenat wird bei 4°C für 10 Minuten bei 1000 g zentrifugiert. Nach anschließender Zentrifugierung bei 17000 g für 55 Minuten erhält man die Synaptosomen (P2-Fraktion), die in 0,32 M Glucose (0,5 mU 100 mg des ursprünglichen Gewichts) noch einmal suspendiert werden.The homogenate is centrifuged at 4 ° C for 10 minutes at 1000 g. After subsequent centrifugation at 17000 g for 55 minutes, the synaptosomes (P 2 fraction) are obtained, which are resuspended in 0.32 M glucose (0.5 mU 100 mg of the original weight).

Der jeweilige Uptake wird in einer 96-well Mikrotiterplatte gemessen. Das Volumen beträgt 250 µl und die Inkubation erfolgt bei Raumtemperatur (ca. 20-25 °C) unter O2 Atmosphäre.The respective uptake is measured in a 96-well microtiter plate. The volume is 250 μl and the incubation is carried out at room temperature (about 20-25 ° C) under O 2 atmosphere.

Die Inkubationszeit beträgt 7,5 Minuten für [3H]-NA und 5 Minuten für [3H]-5-HT. Anschließend werden die 96 Proben durch eine Unifilter GF/B® Mikrotiterplatte (Packard) filtriert und mit 200 mL inkubierten Puffer mit Hilfe eines "Brabdel Cell-Harvester MPXRI-96T" gewaschen. Die Unifilter GF/B Platte wird bei 55°C 1 Stunde getrocknet. Im Anschluß wird die Platte mit einem Back seal® (Packard) verschlossen und mit 35 µl Szintilationsflüssigkeit pro Well (Ultima Gold®, Packard) versetzt. Nach dem Verschließen mit einem top seal® (Packard) wird, nach der Einstellung des Gleichgewichts (etwa 5 Stunden), die Radioaktivität in einem "Trilux 1450 Microbeta" (Wallac, Freiburg, Deutschland) bestimmt.The incubation time is 7.5 minutes for [ 3 H] -NA and 5 minutes for [ 3 H] -5-HT. The 96 samples are filtered through a Unifilter GF / B ® microtiter plate (Packard) and incubated with 200 mL buffer using a washed "Brabdel Cell Harvester MPXRI-96T". The Unifilter GF / B plate is dried at 55 ° C for 1 hour. Subsequently, the plate is sealed with a back seal ® (Packard) with 35 ul scintillation fluid per well (Ultima Gold ®, Packard) was added. After sealing with a top seal ® (Packard), the radioactivity in a "Trilux 1450 Microbeta" (Wallac, Freiburg, Germany), after adjustment of the equilibrium (around 5 hours), determined.

Die Menge des bei der vorstehenden Bestimmung eingesetzten Proteins entspricht den aus der Literatur bekannten Werten, wie z.B. in " Protein measurement with the folin phenol reagent", Lowry et al., J. Biol. Chem., 193, 265-275, 1951 beschrieben.The amount of the protein used in the above determination corresponds to the values known from the literature, such as in " Protein measurement with the folinophenol reagent ", Lowry et al., J. Biol. Chem., 193, 265-275, 1951 described.

Eine detaillierte Methodenbeschreibung kann ferner auch der Literatur, beispielsweise aus M.Ch. Frink, H.-H. Hennies, W. Engelberger, M. Haurand und B. Wilffert (1996) Arzneim.-Forsch./Drug Res. 46 (III), 11, 1029-1036 , entnommen werden. Folgende Kenndaten wurden für den NA- bzw. 5-HT-Transporter ermittelt: N ⁢ A - U ⁢ p ⁢ t ⁢ a ⁢ k ⁢ e : K ⁢ m = 0 , 32 ± 0 , 11 μ ⁢ M

Figure imgb0013
5 ⁢ H ⁢ T - U ⁢ p ⁢ t ⁢ a ⁢ k ⁢ e : K ⁢ m = 0 , 084 ± 0 , 011 μ ⁢ M
Figure imgb0014
 A detailed description of the method can also be found in the literature, for example M.Ch. Frink, H.-H. Hennies, W. Engelberger, M. Haurand and B. Wilffert (1996) Arzneim.-Forsch./Drug Res. 46 (III), 11, 1029-1036 , are taken. The following characteristics were determined for the NA or 5-HT transporter: N ⁢ A - U ⁢ p ⁢ t ⁢ a ⁢ k ⁢ e : K ⁢ m = 0 . 32 ± 0 . 11 μ ⁢ M
Figure imgb0013
 5 ⁢ H ⁢ T - U ⁢ p ⁢ t ⁢ a ⁢ k ⁢ e : K ⁢ m = 0 . 084 ± 0 . 011 μ ⁢ M
Figure imgb0014

IV. Methode zur Bestimmung der Affinität zur Batrachotoxin-(BTX)-Bindungsstelle des Natriumkanals:IV. Method for Determining the Affinity to the Batrachotoxin (BTX) Binding Site of the Sodium Channel:

Die Bindungsstelle 2 des Natriumkanals ist die sogenannte Batrachotoxin-(BTX) Bindungsstelle. Als Ligand wird [3H]-Batrachotoxinin A20 α-Benzoat (10 nM im Ansatz) eingesetzt. Die lonenkanal-Partikel (Synaptosomen) werden aus dem Ratten Cerebrocortex angereichert, wie in der Veröffentlichung von Gray und Whittaker, 1962, J. Anat. 76, 79-88 beschrieben. Die entsprechende Beschreibung wird hiermit als Referenz eingeführt und gilt als Teil der vorliegenden Offenbarung. Als unspezifische Bindung ist die Radioaktivität definiert, die in Gegenwart von Veratridin (3 x 10-4 M im Ansatz) gemessen wird.The binding site 2 of the sodium channel is the so-called batrachotoxin (BTX) binding site. The ligand used is [ 3 H] -batrachotoxin A20 α-benzoate (10 nM in the reaction mixture). The ion channel particles (synaptosomes) are enriched from the rat cerebrocortex, as in the publication of Gray and Whittaker, 1962, J. Anat. 76, 79-88 described. The corresponding description is hereby incorporated by reference and is considered part of the present disclosure. Unspecific binding is defined as the radioactivity which is measured in the presence of veratridine (3 × 10 -4 M in the reaction).

Die Assaybedingungen werden entsprechend der Veröffentlichung von Pauwels, Leysen und Laduron durchgeführt, wie in Eur. J. Pharmacol. 124, 291-298 beschrieben. Die entsprechende Beschreibung wird hiermit als Referenz eingeführt und gilt als Teil der vorliegenden Offenbarung.The assay conditions are performed according to the publication by Pauwels, Leysen and Laduron, as in Eur. J. Pharmacol. 124, 291-298 described. The corresponding description is hereby incorporated by reference and is considered part of the present disclosure.

Abweichend von dieser Vorschrift wird der Gesamtansatz auf 250 µl verkleinert, so daß der Assay auf 96-well Mikrotiterplatten durchgeführt werden kann. Die Inkubationszeit in diesen Mikrotiterplatten beträgt zwei Stunden bei Raumtemperatur (ca. 20-25°C).Notwithstanding this rule, the total batch is reduced to 250 .mu.l, so that the assay can be carried out on 96-well microtiter plates. The incubation time in these microtiter plates is two hours at room temperature (about 20-25 ° C).

Folgende Kenndaten wurden für den KD-Wert der Bindungsstelle ermittelt:

  • KD: 24,63 ± 1,56 nM.
The following characteristics were determined for the K D value of the binding site:
  • K D : 24.63 ± 1.56 nM.

Im folgenden wird die Erfindung anhand von Beispielen erläutert. Diese Erläuterungen sind lediglich beispielhaft und schränken den allgemeinen Erfindungsgedanken nicht ein.In the following the invention will be explained by way of examples. These explanations are merely exemplary and do not limit the general inventive concept.

Beispiele:Examples:

Die Ausbeuten der hergestellten Verbindungen sind nicht optimiert.The yields of the compounds produced are not optimized.

Alle Temperaturen sind unkorrigiert.All temperatures are uncorrected.

Die Angabe "Ether" bedeutet Diethylether, "EE" Ethylacetat, "DCM" Dichlormethan, "DMF" Dimethylformamid, "DME" Dimethoxyethan"DMSO" Dimethylsulfoxid und "THF" Tetrahydrofuran. Die Angabe "Äquivalente" bedeutet Stoffmengenäquivalente, "Smp." Schmelzpunkt bzw. Schmelzbereich, "Zers." Zersetzung, "RT" Raumtemperatur , "abs." absolut (wasserfrei), ,"rac." racemisch, "konz." konzentriert, "min" Minuten, "h" Stunden, "d" Tage, "Vol.%" Volumenprozent, "m%" Massenprozent und "M" ist eine Konzentrationsangabe in mol/l.The term "ether" means diethyl ether, "EE" ethyl acetate, "DCM" dichloromethane, "DMF" dimethylformamide, "DME" dimethoxyethane "DMSO" dimethyl sulfoxide and "THF" tetrahydrofuran. The term "equivalents" means equivalent molar amounts, "m.p." Melting point or melting range, "Zers." Decomposition, "RT" room temperature, "abs." absolute (anhydrous),, "rac." racemic, "conc." concentrated, "min" minutes, "h" hours, "d" days, "vol.%" volume percent, "m%" mass percent and "M" is a concentration in mol / l.

Die eingesetzten Chemikalien und Lösungsmittel wurden kommerziell bei den herkömmlichen Anbietern (beispielsweise Acros, Acocado, Aldrich, Bachem, Fluka, Lancaster, Maybridge, Merck, Sigma, Tci etc) erworben oder nach üblichen, dem Fachmann bekannten Methoden synthetisiert.The chemicals and solvents used were purchased commercially from conventional suppliers (for example, Acros, Acocado, Aldrich, Bachem, Fluka, Lancaster, Maybridge, Merck, Sigma, Tci, etc.) or synthesized by conventional methods known to those skilled in the art.

Als stationäre Phase für die Säulenchromatographie wurde Kieselgel 60 (0.040 - 0.063 mm) der Firma E. Merck, Darmstadt, eingesetzt.The stationary phase used for the column chromatography was silica gel 60 (0.040-0.063 mm) from E. Merck, Darmstadt.

Die dünnschicht-chromatographischen Untersuchungen wurden mit HPTLC-Fertigplatten, Kieselgel 60 F 254, der Firma E. Merck, Darmstadt, durchgeführt.The thin-layer chromatographic investigations were carried out with HPTLC precast plates, Kieselgel 60 F 254, from E. Merck, Darmstadt.

Die Mischungsverhältnisse von LaufmitteIn für chromatographische Untersuchungen sind stets in Volumen/Volumen angegeben.Run Mixture ratios for chromatographic analyzes are always given in volume / volume.

Die Analytik erfolgte mittels HPLC-MS oder/und NMR.The analysis was carried out by means of HPLC-MS or / and NMR.

Die Numerierung der nachfolgenden Beispielverbindungen stimmt nicht mit der Numerierung der vorstehend explizit angegebenen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen überein.The numbering of the following example compounds does not match the numbering of the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds explicitly mentioned above.

Die Herstellung der substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen gemäß den Beispielen 1-36 erfolgte gemäß dem allgemeinen Herstellungsverfahren 1, welches nachstehend schematisch wiedergegeben ist:The preparation of the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds according to Examples 1-36 was carried out according to the general preparation process 1, which is shown schematically below:

Allgemeines Verfahren I:General Procedure I:

Figure imgb0015
Im folgenden ist die Herstellung einzelner Reaktanden beispielhaft wiedergegeben:
Figure imgb0015
 In the following the production of individual reactants is exemplified:

a) Herstellung von 1-(2-Ethyl-butyryl)-piperidin-4-ona) Preparation of 1- (2-ethyl-butyryl) -piperidin-4-one

Zu einer Lösung von Piperidon Hydrochlorid (4.0 g, 26 mmol) in CH2Cl2 (20 ml) wurde Triethylamin (5.8 g, 57.3 mmol) und eine katalytische Menge DMAP gegeben. Nach Abkühlung auf -10°C wurde 2-Ethylbutyrchlorid (3.9 g, 28.6 mmol) gelöst in CH2Cl2 (10 ml) langsam zugegeben und für 16 h bei RT gerührt. Zur Suspension gab man 5M Kalilauge (25 ml), die organische Phase wurde abgetrennt und die wässerige Phase mit CH2Cl2 (3 x 10 ml) extrahiert. Nach Trocknung der vereinigten organischen Phasen über Na2SO4, Filtration und Entfernung des Lösungsmittels erhielt man das Produkt 1-(2-Ethyl-butyryl)-piperidin-4-on mit einer Ausbeute von 4.3 g (84 % der Theorie).To a solution of piperidone hydrochloride (4.0 g, 26 mmol) in CH 2 Cl 2 (20 mL) was added triethylamine (5.8 g, 57.3 mmol) and a catalytic amount of DMAP. After cooling to -10 ° C., 2-ethylbutyryl chloride (3.9 g, 28.6 mmol) dissolved in CH 2 Cl 2 (10 ml) was slowly added and stirred at RT for 16 h. To the suspension was added 5M potassium hydroxide solution (25 ml), the organic phase was separated and the aqueous phase extracted with CH 2 Cl 2 (3 x 10 ml). After drying the combined organic phases over Na 2 SO 4 , filtration and removal of the solvent, the product 1- (2-ethyl-butyryl) -piperidin-4-one was obtained in a yield of 4.3 g (84% of theory).

b) Herstellung von 1-(4-Chlor-benzoyl)-piperidin-4-onb) Preparation of 1- (4-chloro-benzoyl) -piperidin-4-one

Zu einer Lösung von Piperidon Hydrochlorid (3.0 g, 19.5 mmol) in CH2Cl2 (20 ml) wurde Triethylamin (4.4 g, 43.0 mmol) und eine katalytische Menge DMAP gegeben. Nach Abkühlung auf - 10°C wurde 4-Chlorbenzoylchlorid (3.8 g, 21.5 mmol)) gelöst in CH2Cl2 (10 ml) langsam zugegeben und für 16 h bei RT gerührt. Zur Suspension gab man 5M Kalilauge (20 ml), die organische Phase wurde abgetrennt und die wässerige Phase mit CH2Cl2 (3 x 10 ml) extrahiert. Nach Trocknung der vereinigten organischen Phasen über Na2SO4, Filtration und Entfernung des Lösungsmittels erhielt man das Produkt 1-(4-Chlor-benzoyl)-piperidin-4-on mit einer Ausbeute von 4.4 g (95 %).To a solution of piperidone hydrochloride (3.0 g, 19.5 mmol) in CH 2 Cl 2 (20 mL) was added triethylamine (4.4 g, 43.0 mmol) and a catalytic amount of DMAP. After cooling to -10 ° C., 4-chlorobenzoyl chloride (3.8 g, 21.5 mmol) dissolved in CH 2 Cl 2 (10 ml) was slowly added and stirred at RT for 16 h. To the suspension was added 5M potassium hydroxide solution (20 ml), the organic phase was separated and the aqueous phase extracted with CH 2 Cl 2 (3 x 10 ml). After drying the combined organic phases over Na 2 SO 4 , filtration and removal of the solvent gave the product 1- (4-chloro-benzoyl) -piperidin-4-one with a yield of 4.4 g (95%).

c) Herstellung von 1-(2,4-Dimethoxy-benzoyl)-piperidin-4-onc) Preparation of 1- (2,4-dimethoxy-benzoyl) -piperidin-4-one

Zu einer Lösung von von 2,4-Dimethoxybenzoesäure (11.8 g, 65.1 mmol) in DMF (25 ml) gab man bei 0°C Piperidon Hydrochlorid (3.0 g, 19.5 mmol) gelöst in DMF (25 ml), N,N-Diisopropylcarbodiimid (8.2 g, 65.1 mmol) und 1-Hydroxybenzotriazol (8.8 g, 65.1 mmol) und ließ 3 h bei 0°C und anschließend 2 d bei RT rühren. Zur Reaktionsmischung wurde wässerige 1 M Na2CO3-Lösung (20 ml) gegeben und mit EE (3 x 20 ml) extrahiert. Nach Trocknung der vereinigten organischen Phasen wurde das Lösungsmittel entfernt und der Rückstand mittels Säulenchromathographie gereinigt. Man erhielt das Produkt 1-(2,4-Dimethoxybenzoyl)-piperidin-4-on mit einer Ausbeute von 2.7 g (39 %).To a solution of 2,4-dimethoxybenzoic acid (11.8 g, 65.1 mmol) in DMF (25 mL) at 0 ° C was added piperidone hydrochloride (3.0 g, 19.5 mmol) dissolved in DMF (25 mL), N, N- Diisopropylcarbodiimide (8.2 g, 65.1 mmol) and 1-hydroxybenzotriazole (8.8 g, 65.1 mmol) and allowed to stir for 3 h at 0 ° C and then for 2 d at RT. To the reaction mixture was added aqueous 1 M Na 2 CO 3 solution (20 ml) and extracted with EA (3 × 20 ml). After drying the combined organic phases the solvent was removed and the residue was purified by column chromatography. The product 1- (2,4-dimethoxybenzoyl) -piperidin-4-one was obtained in 2.7 g (39%) yield.

Beispiel 1: 3-(S)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 1: 3- ( S ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one

Eine Lösung von 1-(2-Ethyl-butyryl)-piperidin-4-on (1.8 g, 9.1 mmol) und (S)-Phenylalaninamid (1.5 g, 9.1 mmol) in EtOH (40 ml) wurde für 2.5 h unter Rückfluß erhitzt und für weitere 16 h bei RT gerührt. Nach Entfernung des Lösungsmittels und Trocknung im Vakuum erhielt man das Produkt 3-(S)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 3.1 g (99 %).A solution of 1- (2-ethyl-butyryl) -piperidin-4-one (1.8 g, 9.1 mmol) and ( S ) -phenylalanine amide (1.5 g, 9.1 mmol) in EtOH (40 mL) was refluxed for 2.5 h heated and stirred for a further 16 h at RT. After removal of the solvent and drying in vacuo, the product 3- ( S ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one was obtained in a yield of 3.1 g (99%).

Beispiel 2: 3-(S)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 2: 3- ( S ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

3-(S)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on (610 mg, 1.8 mmol) wurde in Ethylmethylketon (5 ml) gelöst, mit Wasser (18 µl) und TMSCI (247 µl) versetzt und über Nacht gerührt. Der dabei ausgefallene Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 3-(S)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 590 mg (87 %).3- ( S ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one (610 mg, 1.8 mmol) was dissolved in ethyl methyl ketone (5 mL) , Water (18 .mu.l) and TMSCI (247 ul) and stirred overnight. The precipitated solid was filtered off, washed with ether and dried in vacuo. The product 3- ( S ) -Benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in a yield of 590 mg (87%). ,

Beispiel 3: 8-(2,4-Dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 3: 8- (2,4-Dimethoxy-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Eine Lösung von 1-(2,4-Dimethoxy-benzoyl)-piperidin-4-on (1.4 g, 5.1 mmol), (S)-Methioninamid Hydrochlorid (950 mg, 5.1 mmol) und Triethylamin (520 mg, 5.1 mmol) in EtOH (40 ml) wurde für 2.5 h unter Rückfluß erhitzt und für weitere 16 h bei RT gerührt. Nach Entfernung des Lösungsmittels wurde zum Rückstand Wasser (25 ml) und CH2Cl2 (25 ml) zugegeben und mit konz. Natronlauge basisch gestellt. Die wässerige Phase wurde mit CH2Cl2 (3 x 20 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Entfernung des Lösungsmittels und Trocknung im Vakuum erhielt man das Produkt 8-(2,4-Dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 1.9 g (95%).A solution of 1- (2,4-dimethoxy-benzoyl) -piperidin-4-one (1.4 g, 5.1 mmol), ( S ) -methioninamide hydrochloride (950 mg, 5.1 mmol) and triethylamine (520 mg, 5.1 mmol) in EtOH (40 ml) was heated at reflux for 2.5 h and stirred for a further 16 h at RT. After removal of the solvent, to the residue was added water (25 ml) and CH 2 Cl 2 (25 ml) and acidified with conc. Sodium hydroxide solution made basic. The aqueous phase was extracted with CH 2 Cl 2 (3 × 20 ml) and the combined organic phases were dried over Na 2 SO 4 . Removal of the solvent and drying in vacuo gave the product 8- (2,4-dimethoxy-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5]. decan-2-one with a yield of 1.9 g (95%).

Beispiel 4: 8-(2,4-Dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 4: 8- (2,4-Dimethoxy-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

8-(2,4-Dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on (300 mg, 0.8 mmol) wurde in Ethylmethylketon (2 ml) gelöst, mit Wasser (8 µl) und TMSCI (106 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert und im Vakuum getrocknet. Man erhielt das Produkt 8-(2,4-Dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 320 mg (97 %).8- (2,4-Dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one (300mg, 0.8mmol) was dissolved in ethyl methyl ketone (2 ml), water (8 μl) and TMSCI (106 μl) added and stirred overnight. The solid was filtered off and dried in vacuo. The product was obtained with 8- (2,4-dimethoxy-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride Yield of 320 mg (97%).

Beispiel 5: 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 5: 3- ( S, R ) -Benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one

Eine Lösung von 1-(2-Ethyl-butyryl)-piperidin-4-on (1.8 g, 9.0 mmol), (S,R)-Phenylalaninamid Hydrochlorid (1.8 g, 9.0 mmol) und Triethylamin (910 mg, 9.0 mmol) in EtOH (40 ml) wurde für 2.5 h unter Rückfluß erhitzt und für weitere 16 h bei RT gerührt. Nach Entfernung des Lösunsmittels wurde zum Rückstand Wasser (25 ml) und CH2Cl2 (25 ml) zugegeben und mit konz. Natronlauge basisch gestellt. Die wässerige Phase wurde mit CH2Cl2 (3 x 20 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Entfernung des Lösungsmittels und Trocknung im Vakuum erhielt man das Produkt 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 2.9 g (96 %).A solution of 1- (2-ethyl-butyryl) -piperidin-4-one (1.8 g, 9.0 mmol), ( S, R ) -phenylalanine amide hydrochloride (1.8 g, 9.0 mmol) and triethylamine (910 mg, 9.0 mmol) in EtOH (40 ml) was heated at reflux for 2.5 h and stirred for a further 16 h at RT. After removal of the solvent, to the residue was added water (25 ml) and CH 2 Cl 2 (25 ml) and acidified with conc. Sodium hydroxide solution made basic. The aqueous phase was extracted with CH 2 Cl 2 (3 × 20 ml) and the combined organic phases were dried over Na 2 SO 4 . Removal of the solvent and drying in vacuo gave the product 3- ( S , R ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one a yield of 2.9 g (96%).

Beispiel 6: 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 6: 3- ( S , R ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on (300 mg, 0.9 mmol) wurde in Ethylmethylketon (2 ml) gelöst, mit Wasser (9 µl) und TMSCI (122 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 300 mg (91 %).3- ( S , R ) -Benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] Decan-2-one (300 mg, 0.9 mmol) was dissolved in ethyl methyl ketone (2 mL ), treated with water (9 .mu.l) and TMSCI (122 .mu.l) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 3- ( S, R ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in a yield of 300 mg (91 %).

Beispiel 7: 8-Acetyl-3-(S)-benzyl-1,4,8-triaza-spiro[4.5]decan-2-on Example 7: 8-Acetyl-3- ( S ) -benzyl-1,4,8-triaza-spiro [4.5] decan-2-one

Eine Lösung von 1-Acetyl-piperidin-4-on (1.5 g, 10.8 mmol) und (S)-Phenylalaninamid (1.8 g, 10.8 mmol) in EtOH (30 ml) wurde für 2.5 h unter Rückfluß erhitzt und für weitere 16 h bei RT gerührt. Nach Entfernung des Lösungsmittels und Trocknung im Vakuum erhielt man das Produkt 8-Acetyl-3-(S)-benzyl-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 3.0 g (99 %).A solution of 1-acetyl-piperidin-4-one (1.5 g, 10.8 mmol) and ( S ) -phenylalanine amide (1.8 g, 10.8 mmol) in EtOH (30 mL) was refluxed for 2.5 h and refluxed for a further 16 h stirred at RT. Removal of the solvent and drying in vacuo gave the product 8-acetyl-3- ( S ) -benzyl-1,4,8-triaza-spiro [4.5] decan-2-one with a yield of 3.0 g (99%). ).

Beispiel 8: 8-Acetyl-3-(S)-benzyl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 8: 8-Acetyl-3- ( S ) -benzyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

8-Acetyl-3-(S)-benzyl-1,4,8-triaza-spiro[4.5]decan-2-on (300 mg, 1.0 mmol) wurde in Ethylmethylketon (2 ml) gelöst, mit Wasser (21 µl) und TMSCI (290 µl) versetzt und über Nacht gerührt. Der dabei ausgefallene Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 8-Acetyl-3-(S)-benzyl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 330 mg (96 %).8-Acetyl-3- ( S ) -benzyl-1,4,8-triaza-spiro [4.5] decan-2-one (300mg, 1.0mmol) was dissolved in ethyl methyl ketone (2ml), washed with water (21μl ) and TMSCI (290 μl) and stirred overnight. The precipitated solid was filtered off, washed with ether and dried in vacuo. The product was 8-acetyl-3- ( S ) -benzyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride in 330 mg (96%) yield.

Beispiel 9: 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 9: 3- ( S , R ) -Benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Eine Lösung von 1-(4-Chlor-benzoyl)-piperidin-4-on (2.1 g, 8.7 mmol), (S,R)-Phenylalaninamid Hydrochlorid (1.8 g, 8.7 mmol) und Triethylamin (880 mg, 8.7 mmol) in EtOH (40 ml) wurde für 2.5 h unter Rückfluß erhitzt und für weitere 16 h bei RT gerührt. Nach Entfernung des Lösunsmittels wurde zum Rückstand Wasser (25 ml) und CH2Cl2 (25 ml) zugegeben und mit konz. Natronlauge basisch gestellt. Die Wässerige Phase wurde mit. CH2Cl2 (3 x 20 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Entfernung des Lösnungsmittels und Trocknung im Vakuum erhielt man das Produkt 3-(S,R)-Benzyl-8-(4-chlorbenzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 3.3 g (98 %).A solution of 1- (4-chlorobenzoyl) -piperidin-4-one (2.1 g, 8.7 mmol), ( S , R ) -phenylalanine amide hydrochloride (1.8 g, 8.7 mmol) and triethylamine (880 mg, 8.7 mmol) in EtOH (40 ml) was heated at reflux for 2.5 h and stirred for a further 16 h at RT. After removal of the solvent, to the residue was added water (25 ml) and CH 2 Cl 2 (25 ml) and acidified with conc. Sodium hydroxide solution made basic. The watery phase was with. Extracted CH 2 Cl 2 (3 x 20 ml) and the combined organic phases over Na 2 SO 4 dried. After removal of the solvent and drying in vacuo, the product 3- ( S , R ) -benzyl-8- (4-chlorobenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one was obtained in a yield of 3.3 g (98%).

Beispiel 10: 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 10: 3- ( S , R ) -Benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (300 mg, 0.8 mmol) wurde in Ethylmethylketon (2 ml) gelöst, mit Wasser (8 µl) und TMSCI (109 µl) versetzt und über Nacht gerührt. Nach Zugabe von Hexan (10 ml) wurde die wässerige Phase abgetrennt und der Rückstand im Vakuum getrocknet. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 260 mg (77 %).3- ( S , R ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (300 mg, 0.8 mmol) was dissolved in ethyl methyl ketone (2 mL ), treated with water (8 .mu.l) and TMSCI (109 .mu.l) and stirred overnight. Hexane (10 ml) was added and the aqueous phase was separated and the residue was dried in vacuo. The product 3- ( S , R ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 260 mg (77 %).

Beispiel 11: 3-(S)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 11: 3- ( S ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Eine Lösung von 1-(4-Chlor-benzoyl)-piperidin-4-on (2.2 g, 9.1 mmol) und (S)-Phenylalaninamid (1.5 g, 9.1 mmol) in EtOH (40 ml) wurde für 2.5 h unter Rückfluß erhitzt und für weitere 16 h bei RT gerührt. Nach Entfernung des Lösungsmittels gab man EE (60 ml) zu und rührte für 1 h bei 40°C. Nach Filtration und Trocknung im Vakuum erhielt man das Produkt 3-(S)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 2.6 g (76 %).A solution of 1- (4-chlorobenzoyl) -piperidin-4-one (2.2 g, 9.1 mmol) and ( S ) -phenylalanine amide (1.5 g, 9.1 mmol) in EtOH (40 mL) was refluxed for 2.5 h heated and stirred for a further 16 h at RT. After removal of the solvent, EA (60 ml) was added and stirred for 1 h at 40 ° C. Filtration and drying in vacuo gave the product 3- ( S ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one with a yield of 2.6 g (76%).

Beispiel 12: 3-(S)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 12: 3- ( S ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

3-(S)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (500 mg, 1.3 mmol) wurde in Ethylmethylketon (4 ml) gelöst, mit Wasser (13 µl) und TMSCI (181 µl) versetzt und über Nacht gerührt. Der dabei ausgefallene Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 3-(S)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 390 mg (72 %).3- ( S ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (500 mg, 1.3 mmol) was dissolved in ethyl methyl ketone (4 ml) , treated with water (13 .mu.l) and TMSCI (181 .mu.l) and stirred overnight. The precipitated solid was filtered off, washed with ether and dried in vacuo. The product 3- ( S ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 390 mg (72%) yield. ,

Beispiel 13: 8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on Example 13: 8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one

Eine Lösung von 1-(2-Ethyl-butyryl)-piperidin-4-on (1.6 g, 8.1 mmol), (S)-Methioninamid Hydrochlorid (1.5 g, 8.1 mmol) und Triethylamin (820 mg, 8.1 mmol) in EtOH (66 ml) wurde für 16 h unter Rückfluß erhitzt. Nach Entfernung des Lösungsmittels wurde zum Rückstand Wasser (50 ml) und CH2Cl2 (50 ml) zugegeben und mit konz. Natronlauge basisch gestellt. Die wässerige Phase wurde mit CH2Cl2 (3 x 20 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Entfernung des Lösungsmittels und Trocknung im Vakuum erhielt man das Produkt 8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on mit einer Ausbeute von 1.8 g (69 %).A solution of 1- (2-ethyl-butyryl) -piperidin-4-one (1.6 g, 8.1 mmol), ( S ) -methioninamide hydrochloride (1.5 g, 8.1 mmol) and triethylamine (820 mg, 8.1 mmol) in EtOH (66 ml) was heated at reflux for 16 h. After removal of the solvent, to the residue was added water (50 ml) and CH 2 Cl 2 (50 ml) and acidified with conc. Sodium hydroxide solution made basic. The aqueous phase was extracted with CH 2 Cl 2 (3 × 20 ml) and the combined organic phases were dried over Na 2 SO 4 . Removal of the solvent and drying in vacuo gave the product 8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decane-2- on with a yield of 1.8 g (69%).

Beispiel 14: 8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on Hydrochlorid Example 14: 8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one hydrochloride

8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on (140 mg, 0.4 mmol) wurde in Ethylmethylketon (1 ml) gelöst, mit Wasser (4 µl) und TMSCI (59 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert und im Vakuum getrocknet. Man erhielt das Produkt 8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triazaspiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 117 mg (75 %).8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one (140 mg, 0.4 mmol) was dissolved in ethyl methyl ketone ( 1 ml), treated with water (4 .mu.l) and TMSCI (59 .mu.l) and stirred overnight. The solid was filtered off and dried in vacuo. The product was 8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triazaspiro [4.5] decan-2-one hydrochloride in 117 mg yield (75%).

Beispiel 15: 1,3-(S)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 15: 1,3- ( S ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 3-(S)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on (1.0 g, 2.9 mmol) in 40 ml trockenem THF gab man bei RT und unter Stickstoff Natriumhydrid (90 mg, 3.8 mmol) hinzu. Nach Rühren für 1 h bei RT wurde langsam Benzylchlorid (1.47 g, 11.6 mmol) zugetropft und erhitzte anschließend 12 h unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (20 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 15 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 1.1 g (52 %).To a solution of 3- ( S ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one (1.0 g, 2.9 mmol) in 40 mL of dry THF was added at RT and under nitrogen to sodium hydride (90 mg, 3.8 mmol). After stirring for 1 h at RT, benzyl chloride (1.47 g, 11.6 mmol) was slowly added dropwise and then heated under reflux for 12 h. After adding an aqueous saturated NH 4 Cl solution (20 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 15 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was done by column chromatography. The product 1,3- ( S ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one was obtained in a yield of 1.1 g (52%). ).

Beispiel 25: 1,3-(S)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 25: 1,3- ( S ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on (654 mg, 1.5 mmol) wurde in Ethylmethylketon (5 ml) gelöst, mit Wasser (15 µl) und TMSCl (210 µl) versetzt und über Nacht gerührt. Anschließend wurde Hexan (10 ml) zugegeben. Der dabei ausgefallene Feststoff wurde abfiltriert und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 671 mg (95 %).1,3- ( S ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one (654 mg, 1.5 mmol) was dissolved in ethyl methyl ketone (5 mL ), added with water (15 .mu.l) and TMSCl (210 .mu.l) and stirred overnight. Subsequently, hexane (10 ml) was added. The precipitated solid was filtered off and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 671 mg (95 %).

Beispiel 16: 8-Acetyl-1,3-(S)-dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on Example 16: 8-Acetyl-1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 8-Acetyl-3-(S)-benzyl-1,4,8-triaza-spiro[4.5]decan-2-on (2.8 g, 9.7 mmol) in 20 ml trockenem THF gab man bei 0°C und unter Stickstoff Natriumhydrid (350 mg, 14.6 mmol) hinzu. Nach Rühren für 1 h bei 0°C wurde langsam Benzylchlorid (1.36 g, 10.7 mmol) zugetropft, ließ auf RT erwärmen und erhitzte anschließend 24 h unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (25 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 20 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 8-Acetyl-1,3-(S)-dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 1.25 g (34 %).To a solution of 8-acetyl-3- ( S ) -benzyl-1,4,8-triaza-spiro [4.5] decan-2-one (2.8 g, 9.7 mmol) in 20 mL of dry THF was added at 0 ° C and under nitrogen sodium hydride (350 mg, 14.6 mmol). After stirring for 1 h at 0 ° C, benzyl chloride (1.36 g, 10.7 mmol) was slowly added dropwise, allowed to warm to RT and then heated under reflux for 24 h. After adding an aqueous saturated NH 4 Cl solution (25 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 20 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product was 8-acetyl-1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one with a yield of 1.25 g (34%).

Beispiel 26: 8-Acetyl-1,3-(S)-dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 26: 8-Acetyl-1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

8-Acetyl-1,3(S)-dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on (1.25 g, 3.3 mmol) wurde in Ethylmethylketon (10 ml) gelöst, mit Wasser (33 µl) und TMSCI (461 µl) versetzt und über Nacht gerührt. Der dabei ausgefallene Feststoff wurde abfiltriert, mit Diethylether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 8-Acetyl-1,3-(S)-dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 939 mg (69 %).8-Acetyl-1,3 ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one (1.25 g, 3.3 mmol) was dissolved in ethyl methyl ketone (10 ml), washed with water (33 μl) and TMSCI (461 μl) and stirred overnight. The precipitated solid was filtered off, washed with diethyl ether and dried in vacuo. The product was 8-acetyl-1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one Hydrochloride with a yield of 939 mg (69%).

Beispiel 17: 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 17: 3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-methoxybenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (920 mg, 2.4 mmol) in 20 ml trockenem THF gab man bei RT und unter Stickstoff Natriumhydrid (90 mg, 3.6 mmol) hinzu. Nach Rühren für 1 h bei RT wurde langsam 4-Methoxybenzylchlorid (410 mg, 2.6 mmol) zugetropft und erhitzte anschließend 48 h unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (15 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 10 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 500 mg (41 %).To a solution of 3- ( S, R ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (920 mg, 2.4 mmol) in 20 In dry THF, sodium hydride (90 mg, 3.6 mmol) was added at RT and under nitrogen. After stirring for 1 h at RT, 4-methoxybenzyl chloride (410 mg, 2.6 mmol) was slowly added dropwise and then heated under reflux for 48 h. After adding an aqueous saturated NH 4 Cl solution (15 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 10 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product 3- ( S, R ) -benzyl-8- (4-chloro-benzoyl) -1- (4-methoxy-benzyl) -1,4,8-triaza-spiro [4.5] decane-2 was obtained. on with a yield of 500 mg (41%).

Beispiel 27: 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 27: 3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-methoxybenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on (500 mg, 1.0 mmol) wurde in Ethylmethylketon (4 ml) gelöst, mit Wasser (10 µl) und TMSCl (138 µl) versetzt und über Nacht gerührt. Anschließend wurde Hexan (10 ml) zugegeben, die wässerige Phase abgetrennt und der Rückstand im Vakuum getrocknet. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 507 mg (92 %).3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-methoxybenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one (500 mg , 1.0 mmol) was dissolved in ethyl methyl ketone (4 ml), water (10 μl) and TMSCl (138 μl) added and stirred overnight. Then hexane (10 ml) was added, the aqueous phase separated and the residue dried in vacuo. The product 3- ( S, R ) -benzyl-8- (4-chloro-benzoyl) -1- (4-methoxy-benzyl) -1,4,8-triaza-spiro [4.5] decane-2 was obtained. on hydrochloride with a yield of 507 mg (92%).

Beispiel 18: 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 18: 3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (920 mg, 2.4 mmol) in 20 ml trockenem THF gab man bei RT und unter Stickstoff Natriumhydrid (90 mg, 3.6 mmol) hinzu. Nach Rühren für 1 h bei RT wurde langsam 4-Fluorbenzylchlorid (380 mg, 2.6 mmol) zugetropft und erhitzte anschließend 48 h unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (15 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 15 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 566 mg (48 %).To a solution of 3- ( S, R ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (920 mg, 2.4 mmol) in 20 ml of dry THF was added at RT and below Add nitrogen to sodium hydride (90 mg, 3.6 mmol). After stirring for 1 h at RT, 4-fluorobenzyl chloride (380 mg, 2.6 mmol) was slowly added dropwise and then heated under reflux for 48 h. After adding an aqueous saturated NH 4 Cl solution (15 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 15 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product was obtained 3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decane-2- on with a yield of 566 mg (48%).

Beispiel 28: 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 28: 3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on (560 mg, 1.1 mmol) wurde in Ethylmethylketon (4 ml) gelöst, mit Wasser (11 µl) und TMSCl (158 µl) versetzt und über Nacht gerührt. Der dabei ausgefallene Feststoff wurde abfiltriert und im Vakuum getrocknet. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 450 mg (75 %).3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one (560 mg , 1.1 mmol) was dissolved in ethyl methyl ketone (4 ml), treated with water (11 μl) and TMSCl (158 μl) and stirred overnight. The precipitated solid was filtered off and dried in vacuo. The product was obtained 3- ( S, R ) -Benzyl-8- (4-chloro-benzoyl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decane-2- on hydrochloride with a yield of 450 mg (75%).

Beispiel 19: 1,3-(S,R)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 19: 1,3- ( S, R ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 3-(S,R)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (920 mg, 2.4 mmol) in 20 ml trockenem THF gab man bei RT und unter Stickstoff Natriumhydrid (90 mg, 3.6 mmol) hinzu. Nach Rühren für 1 h bei RT wurde langsam Benzylchlorid (330 mg, 2.6 mmol) zugetropft und erhitzte anschließend 48 h unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (15 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 10 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 1,3-(S,R)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 375 mg (33%).To a solution of 3- ( S, R ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (920 mg, 2.4 mmol) in 20 In dry THF, sodium hydride (90 mg, 3.6 mmol) was added at RT and under nitrogen. After stirring for 1 h at RT, benzyl chloride (330 mg, 2.6 mmol) was slowly added dropwise and then heated under reflux for 48 h. After adding an aqueous saturated NH 4 Cl solution (15 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 10 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product 1,3- ( S, R ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one was obtained in 375 mg ( 33%).

Beispiel 29: 1,3-(S,R)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 29: 1,3- ( S, R ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S,R)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (370 mg, 0.8 mmol) wurde in Ethylmethylketon (3 ml) gelöst, mit Wasser (8 µl) und TMSCI (109 µl) versetzt und über Nacht gerührt. Der dabei ausgefallene Feststoff wurde abfiltriert und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S,R)-Dibenzyl-8-(4-chlorbenzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 355 mg (89 %).1,3- ( S, R ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (370 mg, 0.8 mmol) was dissolved in ethyl methyl ketone ( 3 ml), treated with water (8 .mu.l) and TMSCI (109 .mu.l) and stirred overnight. The precipitated solid was filtered off and dried in vacuo. The product 1,3- ( S, R ) -dibenzyl-8- (4-chlorobenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 355 mg (89 %).

Beispiel 20: 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 20: 3- ( S, R ) -Benzyl-8- (2-ethyl-butyryl) -1- (4-methoxybenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on (850 mg, 2.5 mmol) in 20 ml trockenem THF gab man bei RT und unter Stickstoff Natriumhydrid (90 mg, 3.6 mmol) hinzu. Nach Rühren für 1 h bei RT wurde langsam 4-Methoxybenzylchlorid (430 mg, 2.7 mmol) zugetropft und erhitzte anschließend 48 h unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (15 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 10 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 563 mg (51 %).To a solution of 3- ( S, R ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one (850 mg, 2.5 mmol) in 20 In dry THF, sodium hydride (90 mg, 3.6 mmol) was added at RT and under nitrogen. After stirring for 1 h at RT, 4-methoxybenzyl chloride (430 mg, 2.7 mmol) was slowly added dropwise and then heated under reflux for 48 h. After adding an aqueous saturated NH 4 Cl solution (15 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 10 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product was obtained 3- ( S, R ) -Benzyl-8- (2-ethyl-butyryl) -1- (4-methoxybenzyl) -1,4,8-triaza-spiro [4.5] decane-2-one. on with a yield of 563 mg (51%).

Beispiel 30: 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 30: 3- ( S, R ) -Benzyl-8- (2-ethylbutyryl) -1- (4-methoxy-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-methoxy-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on (550 mg, 1.2 mmol) wurde in Ethylmethylketon (4 ml) gelöst, mit Wasser (12 µl) und TMSCI (169 µl) versetzt und über Nacht gerührt. Anschließend wurde Hexan (10 ml) zugegeben, die wässerige Phase abgetrennt und der Rückstand im Vakuum getrocknet. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-methoxybenzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 530 mg (90%).3- ( S, R ) -benzyl-8- (2-ethyl-butyryl) -1- (4-methoxybenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one (550 mg , 1.2 mmol) was dissolved in ethyl methyl ketone (4 ml), treated with water (12 μl) and TMSCl (169 μl) and stirred overnight. Then hexane (10 ml) was added, the aqueous phase separated and the residue dried in vacuo. The product was obtained 3- ( S, R ) -benzyl-8- (2-ethyl-butyryl) -1- (4-methoxybenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one Hydrochloride with a yield of 530 mg (90%).

Beispiel 21: 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 21: 3- ( S, R ) -Benzyl-8- (2-ethylbutyryl) -1- (4-fluorobenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on (850 mg, 2.5 mmol) in 20 ml trockenem THF gab man bei RT und unter Stickstoff Natriumhydrid (90 mg, 3.6 mmol) hinzu. Nach Rühren für 1 h bei RT wurde langsam 4-Fluorbenzylchlorid (390 mg, 2.7 mmol) zugetropft und erhitzte anschließend 48 h unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (15 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 10 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 861 mg (75 %).To a solution of 3- ( S, R ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one (850 mg, 2.5 mmol) in 20 In dry THF, sodium hydride (90 mg, 3.6 mmol) was added at RT and under nitrogen. After stirring for 1 h at RT, 4-fluorobenzyl chloride (390 mg, 2.7 mmol) was slowly added dropwise and then heated under reflux for 48 h. After adding an aqueous saturated NH 4 Cl solution (15 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 10 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product was obtained 3- ( S, R ) -benzyl-8- (2-ethyl-butyryl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decane-2- on with a yield of 861 mg (75%).

Beispiel 31: 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 31: 3- ( S, R ) -Benzyl-8- (2-ethylbutyryl) -1- (4-fluorobenzyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on (850 mg, 1.2 mmol) wurde in Ethylmethylketon (7 ml) gelöst, mit Wasser (18 µl) und TMSCI (255 µl) versetzt und über Nacht gerührt. Anschließend wurde Hexan (10 ml) zugegeben, die wässerige Phase abgetrennt und der Rückstand im Vakuum getrocknet. Man erhielt das Produkt 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1-(4-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 853 mg (95 %).3- ( S, R ) -Benzyl-8- (2-ethyl-butyryl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one (850 mg , 1.2 mmol) was dissolved in ethyl methyl ketone (7 ml), water (18 μl) and TMSCI (255 μl) added and stirred overnight. Then hexane (10 ml) was added, the aqueous phase separated and the residue dried in vacuo. The product was obtained 3- ( S, R ) -benzyl-8- (2-ethyl-butyryl) -1- (4-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decane-2- on hydrochloride with a yield of 853 mg (95%).

Beispiel 22: 1,3-(S,R)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 22: 1,3- ( S, R ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 3-(S,R)-Benzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on (850 mg, 2.5 mmol) in 20 ml trockenem THF gab man bei RT und unter Stickstoff Natriumhydrid (90 mg, 3.6 mmol) hinzu. Nach Rühren für 1 h bei RT wurde langsam Benzylchlorid (340 mg, 2.7 mmol) zugetropft und erhitzte anschließend 48 h unter Rückfluß. Es wurde Benzylchlorid (170 mg, 1.4 mmol) zugegeben und für weitere 16 h unter Rückfluß erhitzt. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (15 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 10 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 1,3-(S,R)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 826 mg (77 %).To a solution of 3- ( S, R ) -benzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one (850 mg, 2.5 mmol) in 20 In dry THF, sodium hydride (90 mg, 3.6 mmol) was added at RT and under nitrogen. After stirring for 1 h at RT slowly added dropwise benzyl chloride (340 mg, 2.7 mmol) and then heated under reflux for 48 h. Benzyl chloride (170 mg, 1.4 mmol) was added and heated at reflux for a further 16 h. After adding an aqueous saturated NH 4 Cl solution (15 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 10 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product 1,3- ( S, R ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one was obtained in 826 mg ( 77%).

Beispiel 32: 1,3-(S,R)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 32: 1,3- ( S, R ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S,R)-Dibenzyl-8-(2-ethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on (810 mg, 1.9 mmol) wurde in Ethylmethylketon (6 ml) gelöst, mit Wasser (18 µl) und TMSCI (260 µl) versetzt und über Nacht gerührt. Der dabei ausgefallene Feststoff wurde abfiltriert und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S,R)-Dibenzyl-8-(2-ethylbutyryl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 685 (78 %).1,3- ( S, R ) -dibenzyl-8- (2-ethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one (810 mg, 1.9 mmol) was dissolved in ethyl methyl ketone ( 6 ml), treated with water (18 μl) and TMSCI (260 μl) and stirred overnight. The precipitated solid was filtered off and dried in vacuo. The product 1,3- ( S, R ) -dibenzyl-8- (2-ethylbutyryl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in a yield of 685 (78%). ).

Beispiel 23: 1-Benzyl-8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 23: 1-Benzyl-8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 8-(2-Ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on (420 mg, 1.3 mmol) in 20 ml trockenem THF gab man bei 0°C und unter Stickstoff Natriumhydrid (50 mg, 1.9 mmol) hinzu. Nach Rühren für 1 h bei 0°C wurde langsam Benzylchlorid (140 mg, 1.4 mmol) zugetropft und erhitzte anschließend 24 h unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (15 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 10 ml) extrahiert und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 1-Benzyl-8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 239 mg (45 %).To a solution of 8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one (420 mg, 1.3 mmol) in 20 ml of dry THF was added at 0 ° C and under nitrogen sodium hydride (50 mg, 1.9 mmol). After stirring for 1 h at 0 ° C, benzyl chloride (140 mg, 1.4 mmol) was slowly added dropwise and then heated under reflux for 24 h. After adding an aqueous saturated NH 4 Cl solution (15 ml), the reaction mixture was filtered off, the filtrate was extracted with EA (3 × 10 ml) and the combined organic phases were dried over Na 2 SO 4 . After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product was obtained with 1-benzyl-8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one a yield of 239 mg (45%).

Beispiel 33: 1-Benzyl-8-(2-ethyl-butyryl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 33: 1-Benzyl-8- (2-ethyl-butyryl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1-Benzyl-8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on (230 mg, 0.6 mmol) wurde in Ethylmethylketon (2 ml) gelöst, mit Wasser (5 µl) und TMSCI (77 µl) versetzt und über Nacht gerührt. Anschließend wurde Hexan (8 ml) zugegeben, die wässerige Phase abgetrennt und der Rückstand im Vakuum getrocknet. Man erhielt das Produkt 1-Benzyl-8-(2-ethyl-butyryl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 246 mg (90 %).1-Benzyl-8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one (230mg, 0.6 mmol) was dissolved in ethyl methyl ketone (2 ml), water (5 μl) and TMSCI (77 μl) added and stirred overnight. Then hexane (8 ml) was added, the aqueous phase separated and the residue dried in vacuo. The product 1-benzyl-8- (2-ethyl-butyryl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained with a yield of 246 mg (90%).

Beispiel 24: 1,3-(S)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 24: 1,3- ( S ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 3-(S)-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (2.1 g, 5.5 mmol) in 20 ml trockenem THF gab man bei 0°C und unter Stickstoff Natriumhydrid (130 mg, 5.5 mmol) hinzu. Nach Rühren für 1 h bei 0°C wurde langsam Benzylchlorid (760 mg, 6.0 mmol) zugetropft, ließ bis auf RT erwärmen und erhitzte anschließend 4 d unter Rückfluß. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (30 ml) wurde die Reaktionsmischung abfiltriert, das Filtrat mit EE (3 x 20 ml) extrahiert, die vereinigten organischen Phasen über Na2SO4 getrocknet und das Lösungsmittels entfernt. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(4-chlorbenzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on als gelbes Öl mit einer Ausbeute von 2.62 g (99 %).To a solution of 3- ( S ) -benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (2.1 g, 5.5 mmol) in 20 ml of dry THF was added at 0 ° C and under nitrogen sodium hydride (130 mg, 5.5 mmol). After stirring for 1 h at 0 ° C, benzyl chloride (760 mg, 6.0 mmol) was slowly added dropwise, allowed to warm to rt and then heated under reflux for 4 d. After adding an aqueous saturated NH 4 Cl solution (30 ml), the reaction mixture was filtered off, the filtrate extracted with EA (3 × 20 ml), the combined organic phases dried over Na 2 SO 4 and the solvent removed. Further purification was carried out by column chromatography. The product 1,3- ( S ) -dibenzyl-8- (4-chlorobenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one was obtained as a yellow oil with a yield of 2.62 g (99 %).

Beispiel 34: 1,3-(S)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 34: 1,3- ( S ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (2.6 g, 5.5 mmol) wurde in Ethylmethylketon (21 ml) gelöst, mit Wasser (54 µl) und TMSCl (763 µl) versetzt und über Nacht gerührt. Anschließend wurde Hexan (10 ml) zugegeben, der Feststoff abfiltriert und im Vakuum getrocknet. Der dabei ausgefallene Feststoff wurde abfiltriert und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 2.53 g (90 %).1,3- ( S ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (2.6 g, 5.5 mmol) was dissolved in ethyl methyl ketone (21 mL ), treated with water (54 .mu.l) and TMSCl (763 .mu.l) and stirred overnight. Then hexane (10 ml) was added, the solid was filtered off and dried in vacuo. The precipitated solid was filtered off and dried in vacuo. The product was obtained 1,3- ( S ) -dibenzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one Hydrochloride with a yield of 2.53 g (90%).

Die Beispiele 35 und 36 wurden unter Einstrahlung von Mikrowellen hergestellt:Examples 35 and 36 were prepared under microwave irradiation: Beispiel 35: 1-Benzyl-8-(2,4-dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 35: 1-Benzyl-8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 8-(2,4-Dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on (400 mg, 1.0 mmol) in 10 ml DMF gab man bei RT und unter Stickstoff Natriumhydrid (40 mg, 1.5 mmol) hinzu. Nach Rühren für 1 h bei RT wurde langsam 4-Fluorbenzylchlorid (160 mg, 1.1 mmol) zugetropft und erhitzte anschließend für 30 min in der Mikrowelle bei 100°C. Nach Zugabe einer wässerigen gesättigten NH4Cl-Lösung (15 ml) wurde mit Ether (3 x 10 ml) extrahiert, die etherische Phase mit wässeriger gesättigter NaHCO3-Lösung (2 x 10 ml) und die vereinigten organischen Phasen über Na2SO4 getrocknet. Nach Abdestillation des Lösungsmittels erhielt man das Rohprodukt als gelbes Öl. Weitere Aufreinigung erfolgte durch Säulenchromathographie. Man erhielt das Produkt 1-Benzyl-8-(2,4-dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on als mit einer Ausbeute von 296 mg (58 %).To a solution of 8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one (400 mg , 1.0 mmol) in 10 ml of DMF were added at RT and under nitrogen sodium hydride (40 mg, 1.5 mmol). After stirring for 1 h at RT, 4-fluorobenzyl chloride (160 mg, 1.1 mmol) was slowly added dropwise and then heated in the microwave at 100 ° C for 30 min. After adding a saturated aqueous solution of NH 4 Cl (15 ml), it was extracted with ether (3 × 10 ml), the ethereal phase washed with aqueous saturated NaHCO 3 solution (2 × 10 ml) and the combined organic phases over Na 2 SO 4 dried. After distilling off the solvent, the crude product was obtained as a yellow oil. Further purification was carried out by column chromatography. The product 1-benzyl-8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decane-2- was obtained. on with a yield of 296 mg (58%).

Beispiel 36: 1-Benzyl-8-(2,4-dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 36: 1-Benzyl-8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1-Benzyl-8-(2,4-dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on (290 mg, 0.6 mmol) wurde in Ethylmethylketon (2 ml) gelöst, mit Wasser (6 µl) und TMSCI (80 µl) versetzt und über Nacht gerührt. Der dabei ausgefallene Feststoff wurde abfiltriert und im Vakuum getrocknet. Man erhielt das Produkt 1-Benzyl-8-(2,4-dimethoxy-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 105 mg (95 %).1-Benzyl-8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one (290 mg , 0.6 mmol) was dissolved in ethyl methyl ketone (2 ml), water (6 μl) and TMSCl (80 μl) added and stirred overnight. The precipitated solid was filtered off and dried in vacuo. The product 1-benzyl-8- (2,4-dimethoxybenzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decane-2- was obtained. on hydrochloride with a yield of 105 mg (95%).

Die Herstellung der substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen gemäß den nachfolgenden Beispielen erfolgte nach dem allgemeinen Herstellungsverfahren II, welches nachstehend schematisch wiedergegeben ist:The preparation of the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds according to the following examples was carried out according to the general preparation process II, which is shown schematically below:

Allgemeines Verfahren II:General procedure II:

Figure imgb0016
Im folgenden ist die Herstellung einiger Edukte beispielhaft wiedergegeben:
Figure imgb0016
 In the following the production of some educts is exemplified:

a) Herstellung von 3-(S)-Benzyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylestera) Preparation of 3- ( S ) -benzyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylic acid tert-butyl ester

Zu einer Lösung von (S)-Phenylalaninamid (4.9 g, 29.8 mmol) in trockenem EtOH (20 ml) gab man N-tert-Butyloxycarbonyl-piperidon (6.0 g, 29.8 mmol) und erhitzte für 2.5 h unter Rückfluß. Das Lösungsmittel wurde abdestilliert und das 3-(S)-Benzyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylester (10.8 g) wurde ohne weitere Aufarbeitung verwendet.To a solution of ( S ) -phenylalanine amide (4.9 g, 29.8 mmol) in dry EtOH (20 mL) was added N-tert-butyloxycarbonyl-piperidone (6.0 g, 29.8 mmol) and heated at reflux for 2.5 h. The solvent was distilled off and the tert-butyl 3- ( S ) -benzyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylate (10.8 g) was used without further work-up.

b) Herstellung von 3-(S)-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylesterb) Preparation of 3- ( S ) - (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylic acid tert-butyl ester

Zu einer Lösung von (S)-Methioninamid Hydrochlorid (5.5 g, 29.8 mmol) in trockenem EtOH (66 ml) gab man N-tert-Butyloxycarbonyl-piperidon (5.9 g, 29.8 mmol), Triethylamin (3.02 g, 29.8 mmol) und erhitzte für 2.5 h unter Rückfluß. Nach Zugabe von Wasser (50 ml) und CH2Cl2 (200 ml) wurde die organische Phase abgetrennt und die wässerige Phase mit CH2Cl2 (3 x 20 ml) extrahiert. Die vereinigten organischen Phasen wurden über Na2SO4 getrocknet. Nach Filtration wurde das Lösungsmittel abdestilliert. Man erhielt 3-(S)-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylester mit einer Ausbeute von 8.0 g (82 %).To a solution of ( S ) -methioninamide hydrochloride (5.5 g, 29.8 mmol) in dry EtOH (66 ml) was added N-tert-butyloxycarbonyl-piperidone (5.9 g, 29.8 mmol), triethylamine (3.02 g, 29.8 mmol) and heated for 2.5 h under reflux. After adding water (50 ml) and CH 2 Cl 2 (200 ml), the organic phase was separated and the aqueous phase extracted with CH 2 Cl 2 (3 x 20 ml). The combined organic phases were dried over Na 2 SO 4 . After filtration, the solvent was distilled off. This gave 3- ( S ) - (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylic acid tert-butyl ester in a yield of 8.0 g (82%). ,

c) Herstellung von 1,3-(S)-Dibenzyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylesterc) Preparation of tert-butyl 1,3- ( S ) -dibenzyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylate

Zu einer Lösung von 3-(S)-Benzyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylester (12.1 g, 35 mmol) in THF (250 ml) gab man bei RT NaH (1,26 g, 52,5 mmol) hinzu. Nach Rühren für 1 h bei 0°C wurde Benzylchlorid (4.9 g, 38.5 mmol) zugetropft, ließ auf RT erwärmen und erhitzte für 60 h unter Rückfluß. Anschließend wurde erneut Benzylchlorid (2.4 g, 19 mmol) zugegeben und für weitere 16 h unter Rückfluß erhitzt. Die Reaktionsmischung wurde mit wässeriger gesättigter NH4Cl-Lösung (20 ml) versetzt und mit EE (3 x 50 ml) extrahiert. Die vereinigte organische Phase wurde über Na2SO4 getrocknet, filtriert und das Lösungsmittel abdestilliert. Die Aufarbeitung erfolgte über Säulenchromathographie und ergab 1,3-(S)-Dibenzyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylester mit einer Ausbeute von 13.5 g (88 %).To a solution of tert-butyl 3- ( S ) -benzyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylate (12.1 g, 35 mmol) in THF (250 mL) NaH (1.26 g, 52.5 mmol) is added at RT. After stirring for 1 h at 0 ° C, benzyl chloride (4.9 g, 38.5 mmol) was added dropwise, allowed to warm to rt and refluxed for 60 h. Benzyl chloride (2.4 g, 19 mmol) was then added again and heated at reflux for a further 16 h. The reaction mixture was added with aqueous saturated NH 4 Cl solution (20 ml) and extracted with EA (3 × 50 ml). The combined organic phase was dried over Na 2 SO 4 , filtered and the solvent distilled off. The work-up was carried out by column chromatography to give 1,3- ( S ) -dibenzyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylic acid tert-butyl ester in a yield of 13.5 g (88%). ).

d) Herstellung von 1-Benzyl-3-(S)-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylesterd) Preparation of tert-butyl 1-benzyl-3- ( S ) - (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylate

Zu einer Suspension von NaH (385 mg, 16,0 mmol) in THF (60 ml) tropfte man bei 0°C eine Lösung von 3-(S)-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylester (4.4 g, 13.4 mmol) in THF (72 ml). gab Nach Rühren für 1 h bei 0°C wurde Benzylchlorid (2.0 g, 16.0 mmol) zugetropft, ließ auf RT erwärmen und erhitzte für 68 h unter Rückfluß. Die Reaktionsmischung wurde mit wässeriger gesättigter NH4Cl-Lösung (20 ml) versetzt, die organische Phase abgetrennt und die wässerige Phase mit EE (3 x 50 ml) extrahiert. Die vereinigte organische Phase wurde über Na2SO4 getrocknet, filtriert und das Lösungsmittel abdestilliert. Die Aufarbeitung erfolgte über Säulenchromathographie und ergab 1-Benzyl-3-(S)-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylester mit einer Ausbeute von 1.6 g (30 %).To a suspension of NaH (385 mg, 16.0 mmol) in THF (60 ml) was added dropwise at 0 ° C a solution of 3- ( S ) - (2-methylsulfanyl-ethyl) -2-oxo-1,4 , 8-triaza-spiro [4.5] tert-butyl decane-8-carboxylate (4.4 g, 13.4 mmol) in THF (72 ml). gave After stirring for 1 h at 0 ° C, benzyl chloride (2.0 g, 16.0 mmol) was added dropwise, allowed to warm to rt and refluxed for 68 h. The reaction mixture was treated with aqueous saturated NH 4 Cl solution (20 ml), the organic phase separated and the aqueous phase extracted with EA (3 × 50 ml). The combined organic phase was dried over Na 2 SO 4 , filtered and the solvent distilled off. The work-up was carried out by column chromatography and gave 1-benzyl-3- ( S ) - (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylic acid tert-butyl ester with a yield of 1.6 g (30%).

Beispiel 37: 1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on Example 37: 1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 1,3-(S)-Dibenzyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylester (13.5 g, 31.0 mmol) in CH2Cl2 (93 ml) wurde TFA (68.5 g, 601 mmol) bei 0°C zugetropft und 15 min bei dieser Temperatur gerührt. Nach Erwärmen auf RT wurde die Reaktionslösung für weitere 2.5 h gerührt. Anschließend wurde die Reaktionslösung mit wässeriger gesättigter NaHCO3-Lösung auf den pH-Wert 7-8 eingestellt, die organische Phase abgetrennt und die wässerige Phase mit CH2Cl2 (2 x 30 ml) extrahiert. Die vereinigte organische Phase wurde über Na2SO4 getrocknet, filtriert und das Lösungsmittel abdestilliert. Die Aufarbeitung erfolgte über Säulenchromathographie und ergab 1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 7.8 g (75 %).To a solution of tert -butyl 1,3- ( S ) -dibenzyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylate (13.5 g, 31.0 mmol) in CH 2 Cl 2 (93 ml) TFA (68.5 g, 601 mmol) was added dropwise at 0 ° C and stirred for 15 min at this temperature. After warming to RT, the reaction solution was stirred for a further 2.5 h. The reaction solution was then adjusted to pH 7-8 with aqueous saturated NaHCO 3 solution, the organic phase was separated off and the aqueous phase was extracted with CH 2 Cl 2 (2 × 30 ml). The combined organic phase was dried over Na 2 SO 4 , filtered and the solvent distilled off. The work-up was carried out by column chromatography, yielding 1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one with a yield of 7.8 g (75%).

Beispiel 38: 1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 38: 1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on (400 mg, 1.2 mmol) wurde in Ethylmethylketon (3 ml) gelöst, mit Wasser (12 µl) und mit TMSCI (166 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 315 mg (71 %).1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one (400mg, 1.2mmol) was dissolved in ethyl methyl ketone (3mL), water (12μl) and with TMSCI (166 μl) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained with a yield of 315 mg (71%).

Beispiel 39: 1-Benzyl-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 39: 1-Benzyl-3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Zu einer Lösung von 1-Benzyl-3-(S)-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonsäure tert-butylester (1.5 g, 3.5 mmol) in CH2Cl2 (10 ml) wurde TFA (7.8 g, 68.0 mmol) bei 0°C zugetropft und 15 min bei dieser Temperatur gerührt. Nach Erwärmen auf RT wurde die Reaktionslösung für weitere 2.5 h gerührt. Anschließend wurde die Reaktionslösung mit wässeriger gesättigter NaHCO3-Lösung auf den pH-Wert 7-8 eingestellt, die organische Phase abgetrennt und die wässerige Phase mit CH2Cl2 (2 x 10 ml) extrahiert. Die vereinigte organische Phase wurde über Na2SO4 getrocknet, filtriert und das Lösungsmittel abdestilliert. Die Aufarbeitung erfolgte über Säulenchromathographie und ergab 1-Benzyl-3-(S)-(2-methylsulfanylethyl)-1,4,8-triaza-spiro[4.5]decan-2-on mit einer Ausbeute von 655 mg (58 %).To a solution of tert-butyl 1-benzyl-3- ( S ) - (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carboxylate (1.5 g, 3.5 mmol) in CH 2 Cl 2 (10 ml) was added dropwise TFA (7.8 g, 68.0 mmol) at 0 ° C and stirred for 15 min at this temperature. After warming to RT, the reaction solution was stirred for a further 2.5 h. The reaction solution was then adjusted to pH 7-8 with aqueous saturated NaHCO 3 solution, the organic phase was separated off and the aqueous phase was extracted with CH 2 Cl 2 (2 × 10 ml). The combined organic phase was dried over Na 2 SO 4 , filtered and the solvent distilled off. The work-up was carried out by column chromatography to give 1-benzyl-3- ( S ) - (2-methylsulfanylethyl) -1,4,8-triaza-spiro [4.5] decan-2-one with a yield of 655 mg (58%). ,

Die Verbindungen gemäß den nachstehenden Beispielen 40-51 wurden gemäß folgender allgemeiner Arbeitsvorschrift erhalten:The compounds according to Examples 40-51 below were obtained according to the following general procedure:

Zu einer Lösung von 1 äq. 1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on oder 1 äq. 1-Benzyl-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on in trockenem CH2Cl2 (5ml pro mmol Amin) gab man 2 äq. Triethylamin, eine katalytische Menge DMAP, kühlte die Reaktionslösung auf 0°C ab und gab dann tropfenweise 1 äq. Säurechlorid gelöst in trockenem CH2Cl2 (6ml pro mmol Säurechlorid) hinzu. Es wurde für 18 h gerührt wobei sich die Reaktionslösung bis auf RT erwärmte. Es wurde wässerige 5M Kalilauge zugegeben (4ml pro 1.2 mmol Amin), die wässerige Phase mit Dichlormethan extrahiert (2 x 5 ml), die vereinigten organischen Phasen mit wässeriger gesättigter NaCl-Lösung (10 ml) gewaschen und die gesammelten organischen Phasen über Na2SO4. Nach Abdestillation des Lösungsmittels erfolgte die weitere Aufreinigung über Säulenchromathographie.To a solution of 1 eq. 1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one or 1 eq. 1-Benzyl-3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one in dry CH 2 Cl 2 (5 mL per mmol of amine) was added 2 eq. Triethylamine, a catalytic amount of DMAP, cooled the reaction to 0 ° C and then added dropwise 1 eq. Acid chloride dissolved in dry CH 2 Cl 2 (6 ml per mmol acid chloride) added. It was stirred for 18 h with the reaction solution warming to RT. Aqueous 5M potassium hydroxide solution was added (4 ml per 1.2 mmol amine), the aqueous phase extracted with dichloromethane (2 x 5 ml), the combined organic phases washed with aqueous saturated NaCl solution (10 ml) and the collected organic phases over Na 2 SO 4 . After distilling off the solvent, the further purification was carried out by column chromatography.

Beispiel 40: 1,3-(S)-Dibenzyl-8-butyryl-1,4,8-triaza-spiro[4.5]decan-2-on Example 40: 1,3- ( S ) -dibenzyl-8-butyryl-1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) Buttersäurechlorid:Butyric acid chloride: 127 mg (1.19 mmol)127 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 263 mg (55 %)263 mg (55%)

Beispiel 41: 1,3-(S)-Dibenzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 41: 1,3- ( S ) -dibenzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzy!-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- (S) -Dibenzy -1,4,8-triaza-spiro [4.5] decan-2-one!: 400 mg (1.19 mmol)400 mg (1.19 mmol) 3-Fluor-4-(trifluormethylbenzoylchlorid):3-Fluoro-4- (trifluoromethylbenzoyl chloride): 270 mg (1.19 mmol)270 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 409 mg (65 %)409 mg (65%)

Beispiel 42: 1,3-(S)-Dibenzyl-8-(2,3-difluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 42: 1,3- ( S ) -dibenzyl-8- (2,3-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) 2,3-Difluorbenzoylchlorid:2,3-difluorobenzoyl chloride: 211 mg (1.19 mmol)211 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 383 mg (68 %)383 mg (68%)

Beispiel 43: 1,3-(S)-Dibenzyl-8-[2-(4-chlor-phenoxy)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on Example 43: 1,3- ( S ) -dibenzyl-8- [2- (4-chloro-phenoxy) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) 4-Chlorphenoxyacetylchlorid:4-Chlorphenoxyacetylchlorid: 245 mg (1.19 mmol)245 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 417 mg (69 %)417 mg (69%)

Beispiel 44: 1,3-(S)-Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro[4.5]decan-2-on Example 44: 1,3- ( S ) -Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) Diphenylacetylchlorid:diphenylacetyl: 275 mg (1.19 mmol)275 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 460 mg (73 %)460 mg (73%)

Beispiel 45: 1,3-(S)-Dibenzyl-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 45: 1,3- ( S ) -dibenzyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) Phenoxyacetylchlorid:phenoxyacetyl: 203 mg (1.19 mmol)203 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 419 mg (75 %)419 mg (75%)

Beispiel 46: 1,3-(S)-Dibenzyl-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 46: 1,3- ( S ) -dibenzyl-8- (3-phenylpropionyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) 3-Phenylpropionylchlorid:3-phenylpropionyl: 201 mg (1.19 mmol)201 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 417 mg (75 %)417 mg (75%)

Beispiel 47: 1,3-(S)-Dibenzyl-8-(naphthalin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 47: 1,3- ( S ) -dibenzyl-8- (naphthalene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) 2-Naphthoylchlorid:2-naphthoyl: 227 mg (1.19 mmol)227 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 411 mg (70 %)411 mg (70%)

Beispiel 48: 1,3-(S)-Dibenzyl-8-(furan-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 48: 1,3- ( S ) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) 2-Furoylchlorid:2-furoyl: 156 mg (1.19 mmol)156 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 365 mg (71 %)365 mg (71%)

Beispiel 49: 1,3-(S)-Dibenzyl-8-(3-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 49: 1,3- ( S ) -dibenzyl-8- (3-methoxybenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- (S) dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) 3-Methoxybenzoylchlorid:3-methoxybenzoyl: 203 mg (1.19 mmol)203 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 404 mg (72 %)404 mg (72%)

Beispiel 50: 1,3-(S)-Dibenzyl-8-(4-fluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 50: 1,3- ( S ) -dibenzyl-8- (4-fluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1,3-(S)-Dibenzyl-1,4,8-triaza-spiro[4.5]decan-2-on:1,3- ( S ) -dibenzyl-1,4,8-triaza-spiro [4.5] decan-2-one: 400 mg (1.19 mmol)400 mg (1.19 mmol) 3-Methoxybenzoylchlorid:3-methoxybenzoyl: 189 mg (1.19 mmol)189 mg (1.19 mmol) Triethylamin:triethylamine: 241 mg (2.39 mmol)241 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 377 mg (69 %)377 mg (69%)

Beispiel 51: 1-Benzyl-8-(4-fluor-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Example 51: 1-Benzyl-8- (4-fluoro-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one

1-Benzyl-3-(S)-(2-methylsulfanyl-ethyl)- 1,4,8-triaza-spiro[4.5]decan-2-on:1-Benzyl-3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one: 200 mg (1.19 mmol)200 mg (1.19 mmol) 3-Methoxybenzoylchlorid:3-methoxybenzoyl: 99 mg (1.19 mmol)99 mg (1.19 mmol) Triethylamin:triethylamine: 127 mg (2.39 mmol)127 mg (2.39 mmol) Ausbeute nach Säulenchromathographie:Yield after column chromatography: 246 mg (89 %)246 mg (89%)

Beispiel 52: 1,3-(S)-Dibenzyl-8-butyryl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 52: 1,3- ( S ) -dibenzyl-8-butyryl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-butyryl-1,4,8-triaza-spiro[4.5]decan-2-on (272 mg, 0.7 mmol) wurde in Ethylmethylketon (2.2 ml) gelöst, mit Wasser (7 µl) und TMSCI (93 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-butyryl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 281 mg (95 %).1,3- ( S ) -Dibenzyl-8-butyryl-1,4,8-triaza-spiro [4.5] decan-2-one (272 mg, 0.7 mmol) was dissolved in ethyl methyl ketone (2.2 mL), washed with water ( 7 μl) and TMSCI (93 μl) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8-butyryl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 281 mg (95%) yield.

Beispiel 53: 1,3-(S)-Dibenzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 53: 1,3- ( S ) -dibenzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (397 mg, 0.8 mmol) wurde in Ethylmethylketon (3.2 ml) gelöst, mit Wasser (7 µl), Ether (30 ml) und mit TMSCI (105 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 11,3-(S)-Dibenzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 396 mg (93 %).1,3- ( S ) -dibenzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (397 mg, 0.8 mmol) was added in Dissolved ethyl methyl ketone (3.2 mL), added water (7 μL), ether (30 mL) and TMSCI (105 μL) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product was the product 11,3- ( S ) -dibenzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride in a yield of 396 mg (93%).

Beispiel 54: 1,3-(S)-Dibenzyl-8-(2,3-difiuor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 54: 1,3- ( S ) -dibenzyl-8- (2,3-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(2,3-difluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (370 mg, 0.8 mmol) wurde in Ethylmethylketon (2.9 ml) gelöst, mit Wasser (8 µl), Ether (30 ml) und mit TMSCI (108 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(2,3-difluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 317 mg (80 %).1,3- ( S ) -dibenzyl-8- (2,3-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (370 mg, 0.8 mmol) was dissolved in ethyl methyl ketone ( 2.9 ml), water (8 μl), ether (30 ml) and TMSCI (108 μl) were added and the mixture was stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8- (2,3-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 317 mg yield (80%).

Beispiel 55: 1,3-(S)-Dibenzyl-8-[2-(4-chlor-phenoxy)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 55: 1,3- ( S ) -dibenzyl-8- [2- (4-chloro-phenoxy) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-[2-(4-chlor-phenoxy)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on (415 mg, 0.8 mmol) wurde in Ethylmethylketon (3.3 ml) gelöst, mit Wasser (8 µl), und mit TMSCI (115 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-[2-(4-chlor-phenoxy)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 385 mg (87 %).1,3- ( S ) -dibenzyl-8- [2- (4-chloro-phenoxy) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one (415 mg, 0.8 mmol) was dissolved in ethyl methyl ketone (3.3 ml), added with water (8 μl), TMSCI (115 μl) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8- [2- (4-chloro-phenoxy) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained with a Yield of 385 mg (87%).

Beispiel 56: 1,3-(S)-Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 56: 1,3- ( S ) -dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro[4.5]decan-2-on (450 mg, 0.8 mmol) wurde in Ethylmethylketon (3.6 ml) gelöst, mit Wasser (8 µl), mit TMSCI (118 µl) und mit Ether (10 ml) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 402 mg (84 %).1,3- ( S ) -Dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro [4.5] decan-2-one (450 mg, 0.8 mmol) was dissolved in ethyl methyl ketone (3.6 mL), washed with water ( 8 μl), TMSCI (118 μl) and ether (10 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8-diphenylacetyl-1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in a yield of 402 mg (84%).

Beispiel 57: 1,3-(S)-Dibenzyl-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 57: 1,3- ( S ) -dibenzyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on (410 mg, 0.9 mmol) wurde in Ethylmethylketon (3.3 ml) gelöst, mit Wasser (9 µl), mit TMSCI (121 µl) und mit Ether (30 ml) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 347 mg (79 %).1,3- ( S ) -dibenzyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one (410 mg, 0.9 mmol) was dissolved in ethyl methyl ketone (3.3 mL ), water (9 μl), TMSCl (121 μl), and ether (30 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product was obtained 1,3- ( S ) -dibenzyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride with a yield of 347 mg (79%).

Beispiel 58: 1,3-(S)-Dibenzyl-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 58: 1,3- ( S ) -dibenzyl-8- (3-phenylpropionyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on (360 mg, 0.8 mmol) wurde in Ethylmethylketon (2.9 ml) gelöst, mit Wasser (8 µl), TMSCI (107 µl) und mit Ether (10 ml) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 323 mg (83 %).1,3- ( S ) -dibenzyl-8- (3-phenylpropionyl) -1,4,8-triaza-spiro [4.5] decan-2-one (360 mg, 0.8 mmol) was dissolved in ethyl methyl ketone (2.9 ml dissolved, added with water (8 .mu.l), TMSCI (107 .mu.l) and with ether (10 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8- (3-phenyl-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in a yield of 323 mg (83 %).

Beispiel 59: 1,3-(S)-Dibenzyl-8-(naphthalin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 59: 1,3- ( S ) -dibenzyl-8- (naphthalene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(naphthalin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on (400 mg, 0.8 mmol) wurde in Ethylmethylketon (3.2 ml) gelöst, mit Wasser (8 µl), TMSCI (114 µl) und mit Ether (20 ml) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(naphthalin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 407 mg (95 %).1,3- ( S ) -Dibenzyl-8- (naphthalene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one (400 mg, 0.8 mmol) was dissolved in ethyl methyl ketone (3.2 mL dissolved, added with water (8 .mu.l), TMSCI (114 .mu.l) and with ether (20 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8- (naphthalene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained with a yield of 407 mg (95 %).

Beispiel 60: 1,3-(S)-Dibenzyl-8-(furan-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 60: 1,3- ( S ) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(furan-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on (365 mg, 0.9 mmol) wurde in Ethylmethylketon (2.9 ml) gelöst, mit Wasser (8 µl), TMSCI (118 µl) und mit Ether (20 ml) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(furan-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 338 mg (85 %).1,3- ( S ) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one (365 mg, 0.9 mmol) was dissolved in ethyl methyl ketone (2.9 ml dissolved, added with water (8 .mu.l), TMSCI (118 .mu.l) and with ether (20 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- (S) -dibenzyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 338 mg (85 %).

Beispiel 61: 1,3-(S)-Dibenzyl-8-(3-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 61: 1,3- ( S ) -dibenzyl-8- (3-methoxybenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(3-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (404 mg, 0.9 mmol) wurde in Ethylmethylketon (3.2 ml) gelöst, mit Wasser (9 µl) und TMSCI (120 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(3-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 358 mg (82 %).1,3- ( S ) -dibenzyl-8- (3-methoxybenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (404 mg, 0.9 mmol) was dissolved in ethyl methyl ketone (3.2 mL ), with water (9 μl) and TMSCI (120 ul) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8- (3-methoxybenzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in 358 mg (82 %).

Beispiel 62: 1,3-(S)-Dibenzyl-8-(4-fluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 62: 1,3- ( S ) -dibenzyl-8- (4-fluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1,3-(S)-Dibenzyl-8-(4-fluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on (254 mg, 0.9 mmol) wurde in Ethylmethylketon (2.0 ml) gelöst, mit Wasser (5 µl), mit TMSCI (77 µl) und mit Ether (20 ml) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1,3-(S)-Dibenzyl-8-(4-fluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 242 mg (88 %).1,3- ( S ) -dibenzyl-8- (4-fluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one (254 mg, 0.9 mmol) was dissolved in ethyl methyl ketone (2.0 mL ), water (5 μl), TMSCI (77 μl) and ether (20 ml) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1,3- ( S ) -dibenzyl-8- (4-fluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained in a yield of 242 mg (88 %).

Beispiel 63: 1-Benzyl-8-(4-fluor-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid Example 63: 1-Benzyl-8- (4-fluoro-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride

1-Benzyl-8-(4-fluor-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on (223 mg, 0.5 mmol) wurde in Ethylmethylketon (1.8 ml) gelöst, mit Wasser (5 µl) und mit TMSCI (70 µl) versetzt und über Nacht gerührt. Der Feststoff wurde abfiltriert, mit Ether gewaschen und im Vakuum getrocknet. Man erhielt das Produkt 1-Benzyl-8-(4-fluor-benzoyl)-3-(S)-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on Hydrochlorid mit einer Ausbeute von 227 mg (94 %).1-Benzyl-8- (4-fluoro-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one (223 mg, 0.5 mmol) was dissolved in ethyl methyl ketone (1.8 ml), treated with water (5 μl) and TMSCI (70 μl) and stirred overnight. The solid was filtered off, washed with ether and dried in vacuo. The product 1-benzyl-8- (4-fluoro-benzoyl) -3- ( S ) - (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one hydrochloride was obtained with a yield of 227 mg (94%).

Die Verbindungen gemäß den nachfolgenden Beispielen wurden analog nach dem vorstehend beschriebenen allgemeinen Herstellungsverfahren II erhalten: Bsp. Verbindung 64 N-[4-(3-Isobutyl-2-oxo-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-8-carbonyl)-phenyl]-acetamid 65 1-(2-Phenoxy-ethyl)-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 66 2-(2-Oxo-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzonitril 67 8-(2,4-Dimethoxy-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 68 2-[8-(2-Ethyl-butyryl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 69 4-(2-Isobutyl-3-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl)-benzonitril 70 8-(6-Chlor-pyridin-3-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 71 2-[8-(2-Methyl-pentanoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 72 1-Benzyl-8-(biphenyl-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 73 3-Isobutyl-8-(5-methyl-isoxazol-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 74 3-Oxo-3-[2-oxo-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]dec-8-yl]-propionsäureethylester 75 8-(2-Chlor-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 76 8-Cyclopentancarbonyl-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 77 8-(Furan-2-carbonyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 78 3-Benzyl-8-(2-ethylsulfanyl-pyridin-3-carbonyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 79 3-Benzyl-8-(4-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 80 8-(2-Benzyloxy-acetyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 81 3-Benzyl-8-(2-methoxy-acetyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 82 8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 83 2-{8-[3-(2-chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl}-benzonitril 84 3-Benzyl-8-(2-chlor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 85 3-Benzyl-8-(3-dimethylamino-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 86 8-(3-Methyl-benzoyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 87 3-Isopropyl-1-(3-methyl-but-2-enyl)-8-(pyridin-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 88 1-Benzyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 89 2-{8-[3-(2-chlor-phenyl)-acryloyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl}-benzonitril 90 8-(3-Chlor-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 91 Essigsäure 2-(2-benzyl-3-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl)-2-oxo-1-phenyl-ethylester 92 8-(3,5-Dimethoxy-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 93 3-Benzyl-8-(isoxazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 94 8-(3-Chlor-thiophen-2-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 95 3-Isopropyl-8-pentafluorbenzoyl-1,4,8-triaza-spiro[4.5]decan-2-on 96 8-(2,5-Dimethyl-furan-3-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 97 1-Butyl-8-[2-(3,4-dimethoxy-phenyl)-acetyl]-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 98 1-Benzyl-3-isopropyl-8-(pyridin-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 99 1,3-Dibenzyl-8-(3-dimethylamino-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 100 5-{2-[1-(4-Fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-ethyl}-imidazolidin-2,4-dion 101 8-(Biphenyl-4-carbonyl)-1-(4-fluor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 102 2-[2-Oxo-8-(2-propyl-pentanoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 103 2-[8-(Furan-2-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 104 8-[2-(4-Chlor-phenoxy)-acetyl]-3-isobutyl-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 105 1,3-Dibenzyl-8-(4-brom-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 106 8-(3-Difluormethylsulfanyl-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 107 8-(2,3-Dimethyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 108 3-Benzyl-8-(2,3-dimethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 109 1-(4-Fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-8-(pyridin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 110 3-Benzyl-8-(3,3-dimethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on 111 2-[8-(3-Dimethylamino-benzoyl)-3-Isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 112 3-[8-(2-Methoxy-acetyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 113 Essigsäure 2-(3-benzyl-1-methyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl)-2-oxo-1-phenyl-ethylester 114 2-[8-[2-(2-Methoxy-ethoxy)-acetyl]-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 115 3-Benzyl-8-[3-(2-chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-1,4,8-triaza-spiro[4.5]decan-2-on 116 8-(2-Chlor-6-fluor-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 117 1-Methyl-3-(2-methylsulfanyl-ethyl)-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on 118 8-(2-Chlor-pyridin-3-carbonyl)-1-(4-fluor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 119 8-(2-Ethyl-butyryl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 120 1-Methyl-3-(2-methylsulfanyl-ethyl)-8-(2-phenoxy-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 121 8-(3-Fluor-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 122 3-Benzyl-8-(naphthalin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 123 8-Cyclohexancarbonyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 124 8-(2-Phenoxy-acetyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 125 4-[1-Butyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzonitril 126 3-Benzyl-8-(3,3-dimethyl-butyryl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 127 3-Benzyl-8-(4-propyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 128 3-Isopropyl-8-(2-phenoxy-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on 129 1-Butyl-8-hexanoyl-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 130 8-(4-Brom-3-methyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 131 8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 132 1-(2-Fluor-benzyl)-3-isobutyl-8-(3-methyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 133 8-(2-Ethyl-hexanoyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 134 3-Benzyl-8-(3,4-difluor-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 135 3-Benzyl-8-(4-ethoxy-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 136 1-Benzyl-8-(6-chlor-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 137 8-(3-Dimethylamino-benzoyl)-1-(3,5-dimethyl-benzyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 138 3-[8-(Benzo[1,3]dioxol-5-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 139 3-Benzyl-1-methyl-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]decan-2-on 140 8-(4-Ethoxy-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 141 3-Benzyl-8-(2-benzyloxy-acetyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 142 8-(3,4-Difluor-benzoyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 143 3-Benzyl-1-methyl-8-(2-methylsulfanyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 144 1-Butyl-8-(4-methoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 145 1,3-Dibenzyl-8-(2-ethylsulfanyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 146 3-Benzyl-8-(3-difluormethylsulfanyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 147 1-(4-Fluor-benzyl)-8-(furan-2-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 148 3-Benzyl-8-(3-fluor-4-methyl-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 149 8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 150 1-Butyl-8-(6-Chlor-2H-chroman-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 151 3-[8-(3-Methoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 152 8-Cyclobutancarbonyl-3-(2-methylsulfanyl-ethyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 153 3-Benzyl-1-butyl-8-(furan-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 154 1-Benzyl-8-(3-chlor-thiophen-2-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 155 3-Benzyl-8-(2,5-bis-trifluormethyl-benzoyl)-1-butyl-1,4,8-triaza-spiro[4.5]decan-2-on 156 8-(3-Chlor-2-fluor-benzoyl)-1-(3,5-dimethyl-benzyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 157 1-Benzyl-8-(2-chlor-pyridin-3-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 158 3-Isobutyl-8-pentafluorbenzoyl-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 159 8-(2-Benzyloxy-acetyl)-1-butyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 160 8-(Furan-2-carbonyl)-3-isobutyl-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 161 1-Butyl-3-(2-methylsulfanyl-ethyl)-8-(4-phenoxy-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on 162 3-Benzyl-8-(6-chlor-pyridin-3-carbonyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 163 1-(2-Fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-8-(2-phenoxy-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 164 1-(2-Fluor-benzyl)-3-isobutyl-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 165 8-[2-(3-Chlor-phenoxy)-acetyl]-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 166 8-(2,3-Dimethyl-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 167 3-Isopropyl-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 168 3-Benzyl-1-methyl-8-(5-methyl-2-phenyl-2H-[1,2,3]triazole-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 169 8-[3-(2-Chlor-phenyl)-5-methyl-isoxazol-4-carbonyl]-1-(3,5-dimethyl-benzyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 170 1-(2-Fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-8-(pyridin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 171 1-Benzyl-3-(2-methylsulfanyl-ethyl)-8-(2-phenoxy-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 172 1,3-Dibenzyl-8-(3-chlor-thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 173 3-Benzyl-8-(4-tert-butyl-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 174 2-[3-Isobutyl-8-(2-methoxy-acetyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 175 3-Benzyl-1-butyl-8-(5-fluor-2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 176 3-Benzyl-8-[2-(4-methoxy-phenyl)-acetyl]-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 177 1,3-Dibenzyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 178 1-Benzyl-3-isopropyl-8-(2-methyl-6-trifluorm ethyl-pyrid in-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 179 1-Benzyl-8-(4-ethoxy-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 180 3-Benzyl-1-butyl-8-cyclohexancarbonyl-1,4,8-triaza-spiro[4.5]decan-2-on 181 3-[8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 182 1-(2-Fluor-benzyl)-3-isobutyl-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]decan-2-on 183 1-Methyl-3-(2-methylsulfanyl-ethyl)-8-(2-propyl-pentanoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 184 3-Benzyl-1-methyl-8-(2-phenoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on 185 3-Isobutyl-1-prop-2-ynyl-8-(3-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 186 3-Benzyl-8-(furan-2-carbonyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 187 1-Methyl-3-(2-methylsulfanyl-ethyl)-8-(naphthalin-1-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 188 3-Benzyl-1-butyl-8-(3-cyclopentyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on 189 1-(3,5-Dimethyl-benzyl)-3-(2-methylsulfanyl-ethyl)-8-pentanoyl-1,4,8-triaza-spiro[4.5]decan-2-on 190 3-Benzyl-1-butyl-8-(2-methoxy-acetyl)-1,4,8-triaza-spiro[4.5]decan-2-on 191 3-Benzyl-8-(3-fluor-4-trifluormethyl-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 192 1-Benzyl-8-(3-difluormethylsulfanyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 193 8-(2-Chlor-6-fluor-3-methyl-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 194 4-[3-Isopropyl-8-(2-methylsulfanyl-pyridin-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 195 8-[2-(2,5-Dimethoxy-phenyl)-acetyl]-1-(2-fluor-benzyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 196 8-(5-tert-Butyl-2-methyl-furan-3-carbonyl)-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 197 8-(2-Cyclopentyl-acetyl)-1-(4-fluor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 198 4-[8-(3,3-Dimethyl-butyryl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 199 3-[8-Cyclopropancarbonyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 200 3-(3-(2-Methylsulfanyl-ethyl)-2-oxo-8-(3-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 201 1-Butyl-8-(2-cyclopentyl-acetyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 202 3-Benzyl-1-butyl-8-(pyridin-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 203 3-Benzyl-8-[3-(2-chlor-phenyl)-acryloyl]-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 204 4-[8-(3-fluor-4-trifluormethyl-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 205 8-[3-(2,6-Dichlor-phenyl)-5-methyl-isoxazol-4-carbonyl]-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 206 1-Butyl-8-cyclohexancarbonyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 207 3-Benzyl-1-butyl-8-(4-iod-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 208 1-Methyl-3-(2-methylsulfanyl-ethyl)-8-[3-(3-trifluormethyl-phenyl)-acryloyl]-1,4,8-triaza-spiro[4.5]decan-2-on 209 1,3-Dibenzyl-8-(4-phenoxy-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on 210 3-Benzyl-8-(2-chlor-6-fluor-benzoyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 211 4-[8-(2-Chlor-pyridin-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 212 8-(2,5-Dimethyl-furan-3-carbonyl)-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 213 8-(Biphenyl-4-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 214 8-(3-Chlor-thiophen-2-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 215 1-(4-Fluor-benzyl)-8-[2-(4-methoxy-phenyl)-acetyl]-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 216 1-Benzyl-3-isopropyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 217 2-[3-Isopropyl-8-(2-methylsulfanyl-pyridin-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 218 3-[8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 219 1-Butyl-8-(2, 5-dimethyl-furan-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 220 8-(3-Cyclopentyl-propionyl)-1-(2-fluor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 221 1-Benzyl-8-(3-cyclopentyl-propionyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 222 3-(2-Methylsulfanyl-ethyl)-8-(4-phenoxy-butyryl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 223 1,3-Dibenzyl-8-(3-phenyl-acryloyl)-1,4,8-triaza-spiro[4.5]decan-2-on 224 3-Benzyl-8-(6-chlor-2-fluor-3-methyl-benzoyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 225 8-[3-(2-Chlor-phenyl)-acryloyl]-3-isopropyl-1-(2-phenoxy-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 226 2-[3-Isopropyl-2-oxo-8-(3-phenyl-acryloyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 227 3-Benzyl-1-methyl-8-(4-methyl-3-nitro-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 228 1-Benzyl-8-(furan-2-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 229 1-Butyl-8-(3,5-dimethoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 230 1,3-Dibenzyl-8-(3,3-dimethyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on 231 8-(2,6-Difluor-3-methyl-benzoyl)-1-methyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 232 2-[8-(2-Chlor-6-fluor-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 233 8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-3-isopropyl-1-(3-methyl-but-2-enyl)-1,4,8-triaza-spiro[4.5]decan-2-on 234 3-Isobutyl-1-prop-2-ynyl-8-(4-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 235 1-Benzyl-8-(2-chlor-6-fluor-3-methyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 236 Benzoesäure 2-(1-benzyl-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl)-benzylester 237 1,3-Dibenzyl-8-(2-phenyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on 238 3-Benzyl-1-methyl-8-(4-nitro-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 239 3-Benzyl-1-methyl-8-(5-methyl-isoxazol-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 240 1-Benzyl-8-(6-chlor-2-fluor-3-methyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 241 1-Benryl-8-(3-fluor-4-trifluormethyl-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 242 3-Benzyl-8-(6-chlor-2H-chroman-3-carbonyl)-1-methyl-1,4,8-triaza-spiro[4.5]decan-2-on 243 3-Benzyl-1-butyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 244 3-Benzyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 245 2-[8-(6-Chlor-2H-chroman-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 246 2-[8-(5-Methyl-isoxazol-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 247 2-[8-(3-Chlor-2-fluor-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 248 4-[8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 249 3-Benzyl-1-butyl-8-(5-tert-butyl-2-methyl-2H-pyrazol-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 250 3-Benzyl-1-butyl-8-(2-chlor-4-trifluormethyl-pyrimidin-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 251 3-Benzyl-8-(5-methyl-isoxazol-3-carbonyl)-1-prop-2-ynyl-1,4,8-triaza-spiro[4.5]decan-2-on 252 4-[8-(2-Chlor-pyridin-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 253 8-(2-tert-Butyl-5-methyl-2H-pyrazol-3-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 254 4-[8-(2-Methylsulfanyl-pyridin-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 255 Essigsäure 4-[8-(4-acetylamino-benzoyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-butylester 256 [8-(4-Acetylamino-benzoyl)-3-benzyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 257 Essigsäure 4-[8-(2-ethylsulfanyl-pyridin-3-carbonyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-butylester 258 4-[8-(4-Methyl-[1,2,3]thiadiazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 259 4-[1-Allyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzolsulfonamid 260 4-(8-Cyclobutancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzoesäuremethylester 261 Essigsäure 2-[1-allyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-ethylester 262 8-(Biphenyl-4-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 263 [3-(2-Methylsulfanyl-ethyl)-2-oxo-8-propionyl-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 264 8-(Benzo[1,3]dioxole-5-carbonyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 265 1-Allyl-8-(biphenyl-4-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 266 [3-Benzyl-8-(biphenyl-4-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 267 [8-(3-Dimethylamino-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 268 3-(2-Oxo-8-pentanoyl-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzonitril 269 4-(8-Cyclopentancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzoesäuremethylester 270 4-[1-(2-Fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-4-oxo-butansäurethylester 271 1-(2-Fluor-benzyl)-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 272 4-[8-(2-Chlor-pyridin-4-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 273 3-[8-(3,5-Bis-trifluormethyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 274 3-Benzyl-1-(2-fluor-benzyl)-8-(2-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 275 8-(Benzo[1,2,5]oxadiazol-5-carbonyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 276 [3-Benzyl-2-oxo-8-(4-sulfamoyl-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 277 3-[2-Oxo-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 278 Essigsäure 2-[1-(4-acetoxy-butyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-1,1-dimethyl-2-oxo-ethylester 279 8-(6-Chlor-pyridin-3-carbonyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 280 8-(2-Ethoxy-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 281 1-Allyl-8-cyclopropancarbonyl-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 282 3-[3-Isopropyl-8-(2-methoxy-acetyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 283 4-(2-Oxo-8-phenylacetyl-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzoesäuremethylester 284 Essigsäure 2-[1-(3-cyano-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-1-phenyl-ethylester 285 1-(2-Fluor-benzyl)-8-(4-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 286 4-(8-Cyclohexancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl)-benzoesäuremethylester 287 1-(2-Fluor-benzyl)-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]decan-2-on 288 [3-Isobutyl-8-(3-methyl-butyryl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 289 1-Allyl-8-(3,3-dimethyl-butyryl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 290 1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(2-methylsulfanyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 291 [3-Isobutyl-8-(2-methyl-pentanoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 292 4-[8-(5-tert-Butyl-2-methyl-furan-3-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 293 (3-Benzyl-8-cyclopropancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl)-essigsäureethylester 294 [3-Benzyl-8-(3-methyl-butyryl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 295 1-(2,6-Dichlor-benzyl)-8-(2,5-dimethyl-furan-3-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 296 1-Allyl-3-isopropyl-8-[2-(3-methoxy-phenyl)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on 297 [8-(4-tert-Butyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 298 3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-(2-phenoxy-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 299 (3-Benzyl-2-oxo-8-pentanoyl-1,4,8-triaza-spiro[4.5]dec-1-yl)-essigsäureethylester 300 8-(2-Chlor-pyridin-4-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro(4.5]decan-2-on 301 [8-(3-Methyl-butyryl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 302 1-Allyl-3-(2-methylsulfanyl-ethyl)-8-pentafluorbenzoyl-1,4,8-triaza-spiro[4.5]decan-2-on 303 1-(2-Fluor-benzyl)-8-(2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 304 8-(Benzo[1,2,5]oxadiazol-5-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 305 4-[8-(4-tert-Butyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzoesäuremethylester 306 [3-Benzyl-2-oxo-8-(1-phenyl-5-propyl-1H-pyrazol-4-carbonyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 307 1-Allyl-3-isopropyl-8-pent-4-enoyl-1,4,8-triaza-spiro[4.5]decan-2-on 308 3-[2-Oxo-8-(2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 309 8-(2-Dimethylamino-acetyl)-1-(3,5-dimethyl-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 310 Essigsäure 4-[8-(2-ethoxy-benzoyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-butylester 311 1-(2-Fluor-benzyl)-8-(3-methoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 312 [8-(Furan-2-carbonyl)-3-isobutyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 313 8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 314 1-(2-Fluor-benzyl)-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 315 [3-Benzyl-8-(2-fluor-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 316 [8-(Isoxazol-5-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 317 1-(2,6-Dichlor-benzyl)-3-isobutyl-8-(4-propyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 318 [8-[2-(2,5-Dimethoxy-phenyl)-acetyl]-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 319 (3-Benzyl-8-cyclobutancarbonyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl)-essigsäureethylester 320 1-(2-Fluor-benzyl)-8-[2-(4-methoxy-phenyl)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on 321 1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 322 [3-(2-Methylsulfanyl-ethyl)-2-oxo-8-(4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 323 1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(1-phenyl-5-propyl-1H-pyrazol-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 324 1-(2,6-Dichlor-benzyl)-8-(2,3-difluor-4-methyl-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 325 1-Allyl-3-isopropyl-8-(2-methyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 326 8-(2-Chlor-5-trifluormethyl-benzoyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 327 1-Allyl-8-[2-(3-methoxy-phenyl)-acetyl]-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 328 1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on 329 [3-Benzyl-8-(2-benzyloxy-acetyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 330 1-Allyl-8-(5-tert-butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 331 Essigsäure 1,1-dimethyl-2-[3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-ethylester 332 Benzoesäure 2-[1-ethoxycarbonylmethyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester 333 1-Allyl-3-isopropyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 334 1-Allyl-8-(2, 5-dimethyl-furan-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 335 1-Allyl-8-(benzo[1,2,5]oxadiazol-5-carbonyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 336 1-(2-Fluor-benzyl)-8-(4-phenoxy-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on 337 1-Allyl-8-(2-cyclopentyl-acetyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 338 [3-Benzyl-8-(naphthalin-2-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 339 8-[3-(2-Chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 340 3-[8-(3,5-Dimethoxy-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 341 3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-(1-phenyl-5-propyl-1H-pyrazol-4-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 342 {3-Benzyl-8-[3-(2-chlor-6-fluor-phenyl)-5-methyl-isoxazol-4-carbonyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl}-essigsäureethylester 343 1-(2-Fluor-benzyl)-8-(3-fluor-4-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 344 [8-(1-(4-Chlor-phenyl)-5-trifluormethyl-1H-pyrazol-4-carbonyl]-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 345 3-[8-(Naphthalin-1-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yimethyl]-benzonitril 346 [8-(3,3-Dimethyl-butyryl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 347 8-Acetyl-3-(2-methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on 348 [3-Benzyl-8-(3-cyano-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 349 8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-1-(2,6-dichlor-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 350 4-[3-Benzyl-1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzonitril 351 4-[3-Benzyl-1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-4-oxo-butyric acid methylester 352 3-(2-Methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 353 [3-Benzyl-8-(isoxazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 354 8-(3-Difluormethylsulfanyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 355 [3-Benzyl-8-(2,3-dimethyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 356 1-(2-Fluor-benzyl)-8-(4-propyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 357 3-[8-(4-lod-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 358 1-(2-Fluor-benzyl)-8-(2-propyl-pentanoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 359 3-[8-(2,6-Difluor-3-methyl-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 360 3-(2-Methylsulfanyl-ethyl)-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 361 Essigsäure 4-[3-isobutyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-butylester 362 8-[2-(4-Chlor-phenoxy)-acetyl]-3-(2-methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on 363 [3-Benzyl-2-oxo-8-(3-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 364 8-(4-Brom-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on 365 [8-(2-Chlor-pyridin-4-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 366 1-Allyl-8-(3,5-dimethoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 367 3-[8-(4-Methyl-3-nitro-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 368 8-(4-tert-Butyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 369 1-Allyl-3-isopropyl-8-(5-methyl-isoxazol-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 370 1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 371 [3-Benzyl-8-(3-cyclopentyl-propionyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 372 3-Benzyl-8-(3,5-difluor-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 373 [3-Benzyl-8-(5-fluor-2-trifluormethyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 374 [3-Benzyl-2-oxo-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 375 Benzoesäure 2-[1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester 376 1-(2-Fluor-benzyl)-8-(2-methyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 377 1-(2-Fluor-benzyl)-8-(2-phenyl-butyryl)-1,4,8-triaza-spiro[4.5]decan-2-on 378 1-Allyl-8-(6-chlor-pyridin-3-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 379 [8-(2,5-Dimethyl-furan-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 380 [8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 381 Benzoesäure 2-[1-allyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester 382 Essigsäure 2-[1-allyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-8-yl]-2-oxo-1-phenyl-ethylester 383 3-[8-(2-Chlor-6-fluor-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 384 3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-(3-phenyl-propionyl)-1,4,8-triaza-spiro[4.5]decan-2-on 385 3-[8-(2,3-Dimethyl-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 386 [8-(5-Fluor-2-trifluormethyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 387 [8-Cyclopentancarbonyl-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 388 [3-(2-Methylsulfanyl-ethyl)-2-oxo-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 389 1-Allyl-8-[1-(4-chlor-phenyl)-5-trifluormethyl-1H-pyrazol-4-carbonyl]-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 390 1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(naphthalin-1-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 391 1-(2-fluor-benzyl)-8-(4-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 392 3-Benzyl-8-(2-benzyloxy-acetyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 393 3-[8-(2-chlor-6-fluor-3-methyl-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 394 1-Aliyl-8-(2-chlor-5-trifluormethyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 395 8-(3-Methyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on 396 1-(3,5-Dimethyl-benzyl)-8-(2-ethyl-butyryl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 397 8-(5-tert-Butyl-2-methyl-2H-pyrazol-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 398 Benzoesäure 2-[1-(3-cyano-benzyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester 399 8-(4-Methyl-3-nitro-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 400 1-(2,6-Dichlor-benzyl)-3-isobutyl-8-(3,4,5-trimethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 401 3-{8-[2-(2-Brom-phenyl)-acetyl]-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl}-benzonitril 402 3-[8-(2,3-Dichlor-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 403 1-Allyl-8-(6-chlor-2H-chroman-3-carbonyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 404 {3-Benzyl-8-[2-(4-methoxy-phenyl)-acetyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl}-essigsäureethylester 405 3-[3-Isopropyl-2-oxo-8-(1-phenyl-5-propyl-1H-pyrazol-4-carbonyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 406 8-(3-Cyclopentyl-propionyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 407 1-Allyl-8-(3-difluormethylsulfanyl-benzoyl)-3-isopropyl-1,4,8-triaza-spiro[4.5]decan-2-on 408 3-[8-(2-chlor-4-nitro-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 409 [8-(2-Ethoxy-benzoyl)-3-(2-methylsulfanyl-ethyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 410 8-(2,5-Bis-trifluormethyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 411 8-(2-Chlor-pyridin-4-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 412 {3-Benzyi-8-[3-(2,6-dichlor-phenyl)-5-methyl-isoxazol-4-carbonyl]-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl}-essigsäureethylester 413 1-(3,5-Dimethyl-benzyl)-3-isobutyl-8-(2-trifluormethyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 414 8-(3,5-Dimethoxy-benzoyl)-3-(2-methylsuifanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 415 Benzoesäure 2-[3-benzyl-1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzylester 416 3-[8-(Benzo[1,2,5]oxadiazol-5-carbonyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 417 [3-(2-Methylsulfanyl-ethyl)-2-oxo-8-(4-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 418 1-Allyl-3-isopropyl-8-[2-(4-methoxy-phenyl)-acetyl]-1,4,8-triaza-spiro[4.5]decan-2-on 419 3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-(4-propyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 420 3-Benzyl-8-(4-tert-butyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 421 1-Allyl-8-(2,6-difluor-3-methyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 422 8-(3,5-Bis-trifluormethyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 423 3-[8-(4-lod-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 424 3-(2-Methylsulfanyl-ethyl)-1-naphthalin-2-ylmethyl-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 425 [3-Benzyl-8-(2-chlor-pyridin-4-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 426 [3-(2-Methylsulfanyl-ethyl)-8-(4-nitro-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 427 8-(2-Ethyl-hexanoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 428 1-(2,6-Dichlor-benzyl)-3-isobutyl-8-(thiophen-2-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 429 [3-Benzyl-8-(2-chlor-4-nitro-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 430 3-Benzyl-8-(3,5-bis-trifluormethyl-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 431 [3-Benzyl-8-(4-brom-3-methyl-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 432 8-Cyclohexancarbonyl-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 433 8-(2,5-Dimethyl-furan-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 434 8-(3-Difluormethylsulfanyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 435 8-(Furan-2-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 436 [3-Benzyl-8-(2,3-difluor-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 438 3-[3-Isopropyl-8-(4-methyl-[1,2,3]thiadiazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 439 3-[8-(3-Chlor-2-fluor-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 440 [3-Benzyl-8-(naphthalin-1-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 441 8-(4-tert-Butyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 442 3-[3-Benzyl-1-(2-fluor-benzyl)-2-oxo-1,4,8-triaza-spiro[4.5]decan-8-carbonyl]-benzonitril 443 1-(2,6-Dichlor-benzyl)-8-(furan-2-carbonyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 444 8-(2,6-Dichlor-benzoyl)-1-(2-fluor-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 445 1-(3,5-Dimethyl-benzyl)-8-(3-fluor-4-trifluormethyl-benzoyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 446 1-(2-Fluor-benzyl)-8-(3-fluor-4-methyl-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 447 1-Allyl-8-(3-cyclopentyl-propionyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 448 8-[2-(3-Chlor-phenoxy)-acetyl]-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4, 8-triaza-spiro[4.5]decan-2-on 449 1-(3,5-Dimethyl-benzyl)-3-isobutyl-8-(2-methylsulfanyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on 450 3-(2-Methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-8-propionyl-1,4,8-triaza-spiro[4.5]decan-2-on 451 3-[8-(3,4-Dimethoxy-benzoyl)-3-isopropyl-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 452 3-(2-Methylsulfanyl-ethyl)-8-(naphthalin-2-carbonyl)-1-naphthalin-2-ylmethyl-1,4,8-triaza-spiro[4.5]decan-2-on 453 8-(6-Chlor-2H-chroman-3-carbonyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 454 {3-Benzyl-2-oxo-8-[3-(3-trifluormethyl-phenyl)-acryloyl]-l,4,8-triaza-spiro[4.5]dec-1-yl}-essigsäureethylester 455 1-(3,5-Dimethyl-benzyl)-3-isobutyl-8-(3-phenyl-acryloyl)-1,4,8-triaza-spiro[4.5]decan-2-on 456 3-[3-Isopropyl-2-oxo-8-(2-phenoxy-propionyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 457 3-[3-Isopropyl-2-oxo-8-(4-trifluormethoxy-benzoyl)-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 458 1-Allyl-3-(2-methylsulfanyl-ethyl)-8-(3-nitro-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 459 [3-Benzyl-8-(3,4-dichlor-benzoyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-yl]-essigsäureethylester 460 1-(2-Fluor-benzyl)-8-[3-(3-trifluormethyl-phenyl)-acryloyl]-1,4,8-triaza-spiro[4.5]decan-2-on 461 1-Allyl-8-(3,5-bis-trifluormethyl-benzoyl)-3-(2-methylsulfanyl-ethyl)-1,4,8-triaza-spiro[4.5]decan-2-on 462 8-(3-Cyclopentyl-propionyl)-3-(2-methylsulfanyl-ethyl)-1-(2-nitro-benzyl)-1,4,8-triaza-spiro[4.5]decan-2-on 465 1-(3,5-Dimethyl-benzyl)-3-isobutyl-8-(4-nitro-benzoyl)-1,4,8-triaza-spiro[4.5]decan-2-on 466 8-(3-Cyclopentyl-propionyl)-1-(3,5-dimethyl-benzyl)-3-isobutyl-1,4,8-triaza-spiro[4.5]decan-2-on 467 3-[3-Isopropyl-8-(isoxazol-5-carbonyl)-2-oxo-1,4,8-triaza-spiro[4.5]dec-1-ylmethyl]-benzonitril 468 3-Benzyl-1-(2-fluor-benzyl)-8-(2-methyl-6-trifluormethyl-pyridin-3-carbonyl)-1,4,8-triaza-spiro[4.5]decan-2-on The compounds according to the following examples were obtained analogously according to the general preparation process II described above: Ex. connection 64 N- [4- (3-isobutyl-2-oxo-1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-8-carbonyl) -phenyl] -acetamide 65 1- (2-phenoxy-ethyl) -8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 66 2- (2-Oxo-8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzonitrile 67 8- (2,4-dimethoxy-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 68 2- [8- (2-ethyl-butyryl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 69 4- (2-isobutyl-3-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl) -benzonitrile 70 8- (6-chloro-pyridine-3-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 71 2- [8- (2-methyl-pentanoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 72 1-Benzyl-8- (biphenyl-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 73 3-isobutyl-8- (5-methyl-isoxazol-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 74 3-oxo-3- [2-oxo-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] dec-8-yl] -propionic acid ethyl ester 75 8- (2-chloro-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 76 8-Cyclopentanecarbonyl-3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 77 8- (furan-2-carbonyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 78 3-Benzyl-8- (2-ethylsulfanyl-pyridine-3-carbonyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 79 3-Benzyl-8- (4-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 80 8- (2-benzyloxy-acetyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 81 3-Benzyl-8- (2-methoxy-acetyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 82 8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 83 2- {8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec-1 ylmethyl} -benzonitrile 84 3-Benzyl-8- (2-chloro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 85 3-Benzyl-8- (3-dimethylamino-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 86 8- (3-methyl-benzoyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 87 3-isopropyl-1- (3-methyl-but-2-enyl) -8- (pyridin-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 88 1-Benzyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 89 2- {8- [3- (2-chloro-phenyl) acryloyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl} -benzonitrile 90 8- (3-chloro-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 91 Acetic acid 2- (2-benzyl-3-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl) -2-oxo-1-phenylethyl ester 92 8- (3,5-dimethoxy-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 93 3-Benzyl-8- (isoxazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 94 8- (3-chloro-thiophene-2-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 95 3-Isopropyl-8-pentafluorobenzoyl-1,4,8-triaza-spiro [4.5] decan-2-one 96 8- (2,5-dimethyl-furan-3-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 97 1-Butyl-8- [2- (3,4-dimethoxy-phenyl) -acetyl] -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 98 1-Benzyl-3-isopropyl-8- (pyridin-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 99 1,3-dibenzyl-8- (3-dimethylamino-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 100 5- {2- [1- (4-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -2 oxo-ethyl} imidazolidine-2,4-dione 101 8- (biphenyl-4-carbonyl) -1- (4-fluoro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 102 2- [2-oxo-8- (2-propyl-pentanoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 103 2- [8- (Furan-2-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 104 8- [2- (4-chloro-phenoxy) -acetyl] -3-isobutyl-1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 105 1,3-dibenzyl-8- (4-bromo-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 106 8- (3-Difluormethylsulfanyl-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 107 8- (2,3-dimethyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 108 3-Benzyl-8- (2,3-dimethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 109 1- (4-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -8- (pyridine-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 110 3-Benzyl-8- (3,3-dimethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one 111 2- [8- (3-dimethylamino-benzoyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 112 3- [8- (2-methoxy-acetyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 113 Acetic acid 2- (3-benzyl-1-methyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl) -2-oxo-1-phenylethyl ester 114 2- [8- [2- (2-methoxy-ethoxy) -acetyl] -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl ] -benzonitrile 115 3-benzyl-8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -1,4,8-triaza-spiro [4.5] decan-2-one 116 8- (2-chloro-6-fluoro-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 117 1-methyl-3- (2-methylsulfanyl-ethyl) -8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one 118 8- (2-chloro-pyridine-3-carbonyl) -1- (4-fluoro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 119 8- (2-ethyl-butyryl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 120 1-methyl-3- (2-methylsulfanyl-ethyl) -8- (2-phenoxy-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 121 8- (3-fluoro-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 122 3-benzyl-8- (naphthalene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 123 8-Cyclohexanecarbonyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 124 8- (2-phenoxy-acetyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 125 4- [1-Butyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl] -benzonitrile 126 3-Benzyl-8- (3,3-dimethyl-butyryl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 127 3-Benzyl-8- (4-propyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 128 3-isopropyl-8- (2-phenoxy-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one 129 1-Butyl-8-hexanoyl-3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 130 8- (4-bromo-3-methyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 131 8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza spiro [4.5] decan-2-one 132 1- (2-fluoro-benzyl) -3-isobutyl-8- (3-methyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 133 8- (2-ethyl-hexanoyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 134 3-Benzyl-8- (3,4-difluoro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 135 3-Benzyl-8- (4-ethoxy-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 136 1-Benzyl-8- (6-chloro-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 137 8- (3-Dimethylamino-benzoyl) -1- (3,5-dimethyl-benzyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 138 3- [8- (Benzo [1,3] dioxole-5-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl ] -benzonitrile 139 3-benzyl-1-methyl-8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] decan-2-one 140 8- (4-ethoxy-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 141 3-Benzyl-8- (2-benzyloxy-acetyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 142 8- (3,4-difluoro-benzoyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 143 3-benzyl-1-methyl-8- (2-methylsulfanyl-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 144 1-butyl-8- (4-methoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 145 1,3-dibenzyl-8- (2-ethylsulfanyl-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 146 3-Benzyl-8- (3-difluormethylsulfanyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 147 1- (4-fluoro-benzyl) -8- (furan-2-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 148 3-Benzyl-8- (3-fluoro-4-methyl-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 149 8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 150 1-butyl-8- (6-chloro-2H-chroman-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 151 3- [8- (3-methoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 152 8-cyclobutanecarbonyl-3- (2-methylsulfanyl-ethyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 153 3-Benzyl-1-butyl-8- (furan-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 154 1-Benzyl-8- (3-chloro-thiophene-2-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 155 3-Benzyl-8- (2,5-bis-trifluoromethyl-benzoyl) -1-butyl-1,4,8-triaza-spiro [4.5] decan-2-one 156 8- (3-chloro-2-fluoro-benzoyl) -1- (3,5-dimethyl-benzyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decane 2-one 157 1-Benzyl-8- (2-chloro-pyridine-3-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 158 3-Isobutyl-8-pentafluorobenzoyl-1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 159 8- (2-benzyloxy-acetyl) -1-butyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 160 8- (furan-2-carbonyl) -3-isobutyl-1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 161 1-Butyl-3- (2-methylsulfanyl-ethyl) -8- (4-phenoxy-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one 162 3-Benzyl-8- (6-chloro-pyridine-3-carbonyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 163 1- (2-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -8- (2-phenoxy-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2- on 164 1- (2-fluoro-benzyl) -3-isobutyl-8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 165 8- [2- (3-chloro-phenoxy) -acetyl] -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 166 8- (2,3-dimethyl-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 167 3-isopropyl-8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 168 3-benzyl-1-methyl-8- (5-methyl-2-phenyl-2H- [1,2,3] triazole-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2 -one 169 8- [3- (2-chloro-phenyl) -5-methyl-isoxazole-4-carbonyl] -1- (3,5-dimethyl-benzyl) -3- (2-methylsulfanyl-ethyl) -1,4, 8-triaza-spiro [4.5] decan-2-one 170 1- (2-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -8- (pyridine-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 171 1-Benzyl-3- (2-methylsulfanyl-ethyl) -8- (2-phenoxy-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 172 1,3-dibenzyl-8- (3-chloro-thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 173 3-Benzyl-8- (4-tert-butyl-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 174 2- [3-isobutyl-8- (2-methoxy-acetyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 175 3-Benzyl-1-butyl-8- (5-fluoro-2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 176 3-benzyl-8- [2- (4-methoxy-phenyl) -acetyl] -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 177 1,3-dibenzyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 178 1-Benzyl-3-isopropyl-8- (2-methyl-6-trifluoromethyl-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 179 1-Benzyl-8- (4-ethoxy-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 180 3-Benzyl-1-butyl-8-cyclohexanecarbonyl-1,4,8-triaza-spiro [4.5] decan-2-one 181 3- [8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8 -triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 182 1- (2-fluoro-benzyl) -3-isobutyl-8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] decan-2-one 183 1-methyl-3- (2-methylsulfanyl-ethyl) -8- (2-propyl-pentanoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 184 3-benzyl-1-methyl-8- (2-phenoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one 185 3-isobutyl-1-prop-2-ynyl-8- (3-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 186 3-Benzyl-8- (furan-2-carbonyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 187 1-methyl-3- (2-methylsulfanyl-ethyl) -8- (naphthalene-1-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 188 3-Benzyl-1-butyl-8- (3-cyclopentyl-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one 189 1- (3,5-dimethyl-benzyl) -3- (2-methylsulfanyl-ethyl) -8-pentanoyl-1,4,8-triaza-spiro [4.5] decan-2-one 190 3-Benzyl-1-butyl-8- (2-methoxy-acetyl) -1,4,8-triaza-spiro [4.5] decan-2-one 191 3-Benzyl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 192 1-Benzyl-8- (3-difluormethylsulfanyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 193 8- (2-chloro-6-fluoro-3-methyl-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 194 4- [3-isopropyl-8- (2-methylsulfanyl-pyridine-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 195 8- [2- (2,5-Dimethoxy-phenyl) -acetyl] -1- (2-fluoro-benzyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 196 8- (5-tert-Butyl-2-methyl-furan-3-carbonyl) -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2- on 197 8- (2-cyclopentyl-acetyl) -1- (4-fluoro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 198 4- [8- (3,3-dimethyl-butyryl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 199 3- [8-Cyclopropanecarbonyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 200 3- (3- (2-methylsulfanyl-ethyl) -2-oxo-8- (3-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 201 1-butyl-8- (2-cyclopentyl-acetyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 202 3-Benzyl-1-butyl-8- (pyridin-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 203 3-benzyl-8- [3- (2-chloro-phenyl) acryloyl] -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 204 4- [8- (3-fluoro-4-trifluoromethyl-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 205 8- [3- (2,6-dichloro-phenyl) -5-methyl-isoxazole-4-carbonyl] -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [ 4.5] decan-2-one 206 1-Butyl-8-cyclohexanecarbonyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 207 3-Benzyl-1-butyl-8- (4-iodo-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 208 1-methyl-3- (2-methylsulfanyl-ethyl) -8- [3- (3-trifluoromethyl-phenyl) acryloyl] -1,4,8-triaza-spiro [4.5] decan-2-one 209 1,3-dibenzyl-8- (4-phenoxy-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one 210 3-Benzyl-8- (2-chloro-6-fluoro-benzoyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 211 4- [8- (2-chloro-pyridine-3-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 212 8- (2,5-dimethyl-furan-3-carbonyl) -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 213 8- (biphenyl-4-carbonyl) -3- (2-methylsulfanyl-ethyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 214 8- (3-chloro-thiophene-2-carbonyl) -3- (2-methylsulfanyl-ethyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 215 1- (4-fluoro-benzyl) -8- [2- (4-methoxy-phenyl) -acetyl] -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decane 2-one 216 1-Benzyl-3-isopropyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 217 2- [3-Isopropyl-8- (2-methylsulfanyl-pyridine-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 218 3- [8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl ] -benzonitrile 219 1-Butyl-8- (2,5-dimethyl-furan-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 220 8- (3-Cyclopentyl-propionyl) -1- (2-fluoro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 221 1-Benzyl-8- (3-cyclopentyl-propionyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 222 3- (2-methylsulfanyl-ethyl) -8- (4-phenoxy-butyryl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 223 1,3-dibenzyl-8- (3-phenyl-acryloyl) -1,4,8-triaza-spiro [4.5] decan-2-one 224 3-Benzyl-8- (6-chloro-2-fluoro-3-methyl-benzoyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 225 8- [3- (2-chloro-phenyl) acryloyl] -3-isopropyl-1- (2-phenoxy-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 226 2- [3-isopropyl-2-oxo-8- (3-phenyl-acryloyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 227 3-benzyl-1-methyl-8- (4-methyl-3-nitro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 228 1-Benzyl-8- (furan-2-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 229 1-butyl-8- (3,5-dimethoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 230 1,3-dibenzyl-8- (3,3-dimethyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one 231 8- (2,6-difluoro-3-methyl-benzoyl) -1-methyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 232 2- [8- (2-chloro-6-fluoro-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] - benzonitrile 233 8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -3-isopropyl-1- (3-methyl-but-2-enyl) -1,4, 8-triaza-spiro [4.5] decan-2-one 234 3-isobutyl-1-prop-2-ynyl-8- (4-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 235 1-Benzyl-8- (2-chloro-6-fluoro-3-methyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 236 Benzoic acid 2- (1-benzyl-3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl) -benzyl ester 237 1,3-dibenzyl-8- (2-phenyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one 238 3-benzyl-1-methyl-8- (4-nitro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 239 3-benzyl-1-methyl-8- (5-methyl-isoxazol-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 240 1-Benzyl-8- (6-chloro-2-fluoro-3-methyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 241 1-Benryl-8- (3-fluoro-4-trifluoromethyl-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 242 3-Benzyl-8- (6-chloro-2H-chroman-3-carbonyl) -1-methyl-1,4,8-triaza-spiro [4.5] decan-2-one 243 3-Benzyl-1-butyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 244 3-Benzyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 245 2- [8- (6-chloro-2H-chroman-3-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 246 2- [8- (5-methyl-isoxazole-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] - benzonitrile 247 2- [8- (3-chloro-2-fluoro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 248 4- [8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl ] benzoate 249 3-Benzyl-1-butyl-8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 250 3-Benzyl-1-butyl-8- (2-chloro-4-trifluoromethyl-pyrimidine-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 251 3-benzyl-8- (5-methyl-isoxazole-3-carbonyl) -1-prop-2-ynyl-1,4,8-triaza-spiro [4.5] decan-2-one 252 4- [8- (2-chloro-pyridine-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 253 8- (2-tert-butyl-5-methyl-2H-pyrazole-3-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 254 4- [8- (2-methylsulfanyl-pyridine-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 255 Acetic acid 4- [8- (4-acetylaminobenzoyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -butyl ester 256 [8- (4-acetylamino-benzoyl) -3-benzyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 257 Acetic acid 4- [8- (2-ethylsulfanyl-pyridine-3-carbonyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -butyl ester 258 4- [8- (4-Methyl- [1,2,3] thiadiazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 259 4- [1-allyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl] -benzenesulfonamide 260 4- (8-cyclobutanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzoic acid methyl ester 261 Acetic acid 2- [1-allyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -2-oxo-ethyl ester 262 8- (biphenyl-4-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 263 [3- (2-methylsulfanyl-ethyl) -2-oxo-8-propionyl-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 264 8- (benzo [1,3] dioxole-5-carbonyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 265 1-Allyl-8- (biphenyl-4-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 266 [3-Benzyl-8- (biphenyl-4-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 267 [8- (3-dimethylamino-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 268 3- (2-oxo-8-pentanoyl-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzonitrile 269 4- (8-cyclopentanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzoic acid methyl ester 270 4- [1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -4-oxo-butansäurethylester 271 1- (2-fluoro-benzyl) -8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 272 4- [8- (2-Chloro-pyridin-4-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 273 3- [8- (3,5-Bis-trifluoromethyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 274 3-benzyl-1- (2-fluoro-benzyl) -8- (2-methoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 275 8- (Benzo [1,2,5] oxadiazol-5-carbonyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2- on 276 [3-benzyl-2-oxo-8- (4-sulfamoyl-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 277 3- [2-oxo-8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 278 Acetic acid 2- [1- (4-acetoxy-butyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -1,1-dimethyl-2-oxo ethyl 279 8- (6-chloro-pyridine-3-carbonyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 280 8- (2-ethoxy-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 281 1-Allyl-8-cyclopropanecarbonyl-3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 282 3- [3-Isopropyl-8- (2-methoxy-acetyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 283 4- (2-oxo-8-phenylacetyl-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzoic acid methyl ester 284 Acetic acid 2- [1- (3-cyano-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -2-oxo-1-phenyl-ethyl ester 285 1- (2-fluoro-benzyl) -8- (4-methoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 286 4- (8-cyclohexanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl) -benzoic acid methyl ester 287 1- (2-fluoro-benzyl) -8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] decan-2-one 288 [3-isobutyl-8- (3-methyl-butyryl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 289 1-Allyl-8- (3,3-dimethyl-butyryl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 290 1-allyl-3- (2-methylsulfanyl-ethyl) -8- (2-methylsulfanyl-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 291 [3-isobutyl-8- (2-methyl-pentanoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 292 4- [8- (5-tert-Butyl-2-methyl-furan-3-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 293 (3-Benzyl-8-cyclopropanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl) -acetic acid ethyl ester 294 [3-benzyl-8- (3-methyl-butyryl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 295 1- (2,6-dichloro-benzyl) -8- (2,5-dimethyl-furan-3-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 296 1-Allyl-3-isopropyl-8- [2- (3-methoxy-phenyl) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one 297 [8- (4-tert-butyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 298 3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8- (2-phenoxy-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2- on 299 (3-Benzyl-2-oxo-8-pentanoyl-1,4,8-triaza-spiro [4.5] dec-1-yl) -acetic acid ethyl ester 300 8- (2-Chloro-pyridin-4-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro (4.5] decan-2-one 301 [8- (3-methyl-butyryl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 302 1-allyl-3- (2-methylsulfanyl-ethyl) -8-pentafluorobenzoyl-1,4,8-triaza-spiro [4.5] decan-2-one 303 1- (2-fluoro-benzyl) -8- (2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 304 8- (Benzo [1,2,5] oxadiazol-5-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 305 4- [8- (4-tert-Butyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzoic acid methyl ester 306 [3-benzyl-2-oxo-8- (1-phenyl-5-propyl-1H-pyrazole-4-carbonyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 307 1-Allyl-3-isopropyl-8-pent-4-enoyl-1,4,8-triaza-spiro [4.5] decan-2-one 308 3- [2-oxo-8- (2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 309 8- (2-Dimethylamino-acetyl) -1- (3,5-dimethyl-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 310 Acetic acid 4- [8- (2-ethoxy-benzoyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -butyl ester 311 1- (2-fluoro-benzyl) -8- (3-methoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 312 [8- (furan-2-carbonyl) -3-isobutyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 313 8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 314 1- (2-fluoro-benzyl) -8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 315 [3-Benzyl-8- (2-fluoro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 316 [8- (isoxazole-5-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 317 1- (2,6-dichloro-benzyl) -3-isobutyl-8- (4-propyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 318 [8- [2- (2,5-Dimethoxy-phenyl) -acetyl] -3- (2-methylsulfanyl-ethyl) dec-1-yl -2-oxo-1,4,8-triaza-spiro [4.5] ] acetic acid ethyl ester 319 (3-Benzyl-8-cyclobutanecarbonyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl) -acetic acid ethyl ester 320 1- (2-fluoro-benzyl) -8- [2- (4-methoxy-phenyl) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one 321 1-allyl-3- (2-methylsulfanyl-ethyl) -8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 322 [3- (2-methylsulfanyl-ethyl) -2-oxo-8- (4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 323 1-allyl-3- (2-methylsulfanyl-ethyl) -8- (1-phenyl-5-propyl-1H-pyrazole-4-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2- on 324 1- (2,6-dichloro-benzyl) -8- (2,3-difluoro-4-methyl-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 325 1-Allyl-3-isopropyl-8- (2-methyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 326 8- (2-chloro-5-trifluoromethyl-benzoyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 327 1-Allyl-8- [2- (3-methoxy-phenyl) -acetyl] -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 328 1-allyl-3- (2-methylsulfanyl-ethyl) -8- (3-phenyl-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one 329 [3-Benzyl-8- (2-benzyloxy-acetyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 330 1-Allyl-8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decane 2-one 331 Acetic acid 1,1-dimethyl-2- [3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8- yl] -2-oxo-ethyl ester 332 Benzoic acid 2- [1-ethoxycarbonylmethyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester 333 1-Allyl-3-isopropyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 334 1-Allyl-8- (2,5-dimethyl-furan-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 335 1-Allyl-8- (benzo [1,2,5] oxadiazol-5-carbonyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 336 1- (2-fluoro-benzyl) -8- (4-phenoxy-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one 337 1-Allyl-8- (2-cyclopentyl-acetyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 338 [3-benzyl-8- (naphthalene-2-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 339 8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 340 3- [8- (3,5-dimethoxy-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 341 3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8- (1-phenyl-5-propyl-1H-pyrazole-4-carbonyl) -1,4,8-triaza-spiro [ 4.5] decan-2-one 342 {3-benzyl-8- [3- (2-chloro-6-fluoro-phenyl) -5-methyl-isoxazole-4-carbonyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec -1-yl} -acetic acid ethyl ester 343 1- (2-fluoro-benzyl) -8- (3-fluoro-4-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 344 [8- (1- (4-chloro-phenyl) -5-trifluoromethyl-1H-pyrazole-4-carbonyl] -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 345 3- [8- (naphthalene-1-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yimethyl] -benzonitrile 346 [8- (3,3-dimethyl-butyryl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 347 8-Acetyl-3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2-one 348 [3-Benzyl-8- (3-cyano-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 349 8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -1- (2,6-dichloro-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 350 4- [3-benzyl-1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl] -benzonitrile 351 4- [3-Benzyl-1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -4-oxo-butyric acid methyl ester 352 3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 353 [3-Benzyl-8- (isoxazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 354 8- (3-Difluormethylsulfanyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 355 [3-Benzyl-8- (2,3-dimethyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 356 1- (2-fluoro-benzyl) -8- (4-propyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 357 3- [8- (4-iodo-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 358 1- (2-fluoro-benzyl) -8- (2-propyl-pentanoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 359 3- [8- (2,6-difluoro-3-methyl-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 360 3- (2-methylsulfanyl-ethyl) -8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 361 Acetic acid 4- [3-isobutyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl ] butyl 362 8- [2- (4-chloro-phenoxy) -acetyl] -3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2- on 363 [3-benzyl-2-oxo-8- (3-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 364 8- (4-bromo-benzoyl) -3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2-one 365 [8- (2-Chloro-pyridin-4-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 366 1-Allyl-8- (3,5-dimethoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 367 3- [8- (4-methyl-3-nitro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 368 8- (4-tert-butyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 369 1-Allyl-3-isopropyl-8- (5-methyl-isoxazol-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 370 1-allyl-3- (2-methylsulfanyl-ethyl) -8- (2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 371 [3-benzyl-8- (3-cyclopentyl-propionyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 372 3-Benzyl-8- (3,5-difluoro-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 373 [3-benzyl-8- (5-fluoro-2-trifluoromethyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 374 [3-benzyl-2-oxo-8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 375 Benzoic acid 2- [1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester 376 1- (2-fluoro-benzyl) -8- (2-methyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 377 1- (2-fluoro-benzyl) -8- (2-phenyl-butyryl) -1,4,8-triaza-spiro [4.5] decan-2-one 378 1-Allyl-8- (6-chloro-pyridine-3-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 379 [8- (2,5-dimethyl-furan-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] - acetate 380 [8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec -1-yl] -acetic acid ethyl ester 381 Benzoic acid 2- [1-allyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester 382 Acetic acid 2- [1-allyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-8-yl] -2-oxo-1-phenylethyl ester 383 3- [8- (2-chloro-6-fluoro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 384 3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8- (3-phenyl-propionyl) -1,4,8-triaza-spiro [4.5] decan-2-one 385 3- [8- (2,3-dimethyl-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 386 [8- (5-fluoro-2-trifluoromethyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 387 [8-cyclopentanecarbonyl-3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 388 [3- (2-methylsulfanyl-ethyl) -2-oxo-8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 389 1-allyl-8- [1- (4-chloro-phenyl) -5-trifluoromethyl-1H-pyrazole-4-carbonyl] -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [ 4.5] decan-2-one 390 1-allyl-3- (2-methylsulfanyl-ethyl) -8- (naphthalene-1-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 391 1- (2-fluoro-benzyl) -8- (4-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 392 3-Benzyl-8- (2-benzyloxy-acetyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 393 3- [8- (2-chloro-6-fluoro-3-methyl-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 394 1-Aliyl-8- (2-chloro-5-trifluoromethyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 395 8- (3-methyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2-one 396 1- (3,5-dimethyl-benzyl) -8- (2-ethyl-butyryl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 397 8- (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza spiro [4.5] decan-2-one 398 Benzoic acid 2- [1- (3-cyano-benzyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester 399 8- (4-methyl-3-nitro-benzoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2- on 400 1- (2,6-dichloro-benzyl) -3-isobutyl-8- (3,4,5-trimethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 401 3- {8- [2- (2-bromo-phenyl) -acetyl] -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl} -benzonitrile 402 3- [8- (2,3-dichloro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 403 1-Allyl-8- (6-chloro-2H-chroman-3-carbonyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 404 {3-benzyl-8- [2- (4-methoxy-phenyl) -acetyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl} -acetic acid ethyl ester 405 3- [3-isopropyl-2-oxo-8- (1-phenyl-5-propyl-1H-pyrazole-4-carbonyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] - benzonitrile 406 8- (3-Cyclopentyl-propionyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 407 1-Allyl-8- (3-difluormethylsulfanyl-benzoyl) -3-isopropyl-1,4,8-triaza-spiro [4.5] decan-2-one 408 3- [8- (2-chloro-4-nitro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 409 [8- (2-ethoxy-benzoyl) -3- (2-methylsulfanyl-ethyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 410 8- (2,5-bis-trifluoromethyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 411 8- (2-Chloro-pyridin-4-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2- on 412 {3-benzyl-8- [3- (2,6-dichloro-phenyl) -5-methyl-isoxazole-4-carbonyl] -2-oxo-1,4,8-triaza-spiro [4.5] dec-1 yl} acetic acid ethyl ester 413 1- (3,5-dimethyl-benzyl) -3-isobutyl-8- (2-trifluoromethyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 414 8- (3,5-dimethoxy-benzoyl) -3- (2-methylsuifanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 415 Benzoic acid 2- [3-benzyl-1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] decane-8-carbonyl] -benzyl ester 416 3- [8- (Benzo [1,2,5] oxadiazol-5-carbonyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 417 [3- (2-methylsulfanyl-ethyl) -2-oxo-8- (4-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 418 1-Allyl-3-isopropyl 8- [2- (4-methoxy-phenyl) -acetyl] -1,4,8-triaza-spiro [4.5] decan-2-one 419 3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8- (4-propyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 420 3-Benzyl-8- (4-tert-butyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 421 1-Allyl-8- (2,6-difluoro-3-methyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 422 8- (3,5-Bis-trifluoromethyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 423 3- [8- (4-iodo-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 424 3- (2-methylsulfanyl-ethyl) -1-naphthalen-2-ylmethyl-8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 425 [3-Benzyl-8- (2-chloro-pyridin-4-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 426 [3- (2-methylsulfanyl-ethyl) -8- (4-nitro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 427 8- (2-ethyl-hexanoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 428 1- (2,6-dichloro-benzyl) -3-isobutyl-8- (thiophene-2-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 429 [3-Benzyl-8- (2-chloro-4-nitro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 430 3-Benzyl-8- (3,5-bis-trifluoromethyl-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 431 [3-Benzyl-8- (4-bromo-3-methyl-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 432 8-cyclohexanecarbonyl-3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 433 8- (2,5-dimethyl-furan-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decane 2-one 434 8- (3-Difluormethylsulfanyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 435 8- (furan-2-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 436 [3-Benzyl-8- (2,3-difluoro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 438 3- [3-isopropyl-8- (4-methyl- [1,2,3] thiadiazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 439 3- [8- (3-chloro-2-fluoro-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 440 [3-benzyl-8- (naphthalene-1-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 441 8- (4-tert-butyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 442 3- [3-benzyl-1- (2-fluoro-benzyl) -2-oxo-1,4,8-triaza-spiro [4.5] decan-8-carbonyl] -benzonitrile 443 1- (2,6-dichloro-benzyl) -8- (furan-2-carbonyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 444 Of 8- (2.6-dichloro-benzoyl) -1- (2-fluoro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 445 1- (3,5-dimethyl-benzyl) -8- (3-fluoro-4-trifluoromethyl-benzoyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 446 1- (2-fluoro-benzyl) -8- (3-fluoro-4-methyl-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 447 1-Allyl-8- (3-cyclopentyl-propionyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 448 8- [2- (3-chloro-phenoxy) -acetyl] -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4, 8-triaza-spiro [4.5] decane 2-one 449 1- (3,5-Dimethyl-benzyl) -3-isobutyl-8- (2-methylsulfanyl-pyridine-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one 450 3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -8-propionyl-1,4,8-triaza-spiro [4.5] decan-2-one 451 3- [8- (3,4-dimethoxy-benzoyl) -3-isopropyl-2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 452 3- (2-methylsulfanyl-ethyl) -8- (naphthalene-2-carbonyl) -1-naphthalen-2-ylmethyl-1,4,8-triaza-spiro [4.5] decan-2-one 453 8- (6-chloro-2H-chroman-3-carbonyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decane 2-one 454 {3-benzyl-2-oxo-8- [3- (3-trifluoromethyl-phenyl) acryloyl] -l, 4,8-triaza-spiro [4.5] dec-1-yl} -acetic acid ethyl ester 455 1- (3,5-dimethyl-benzyl) -3-isobutyl-8- (3-phenyl-acryloyl) -1,4,8-triaza-spiro [4.5] decan-2-one 456 3- [3-isopropyl-2-oxo-8- (2-phenoxy-propionyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 457 3- [3-isopropyl-2-oxo-8- (4-trifluoromethoxy-benzoyl) -1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 458 1-allyl-3- (2-methylsulfanyl-ethyl) -8- (3-nitro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 459 [3-Benzyl-8- (3,4-dichloro-benzoyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-yl] -acetic acid ethyl ester 460 1- (2-fluoro-benzyl) -8- [3- (3-trifluoromethyl-phenyl) acryloyl] -1,4,8-triaza-spiro [4.5] decan-2-one 461 1-Allyl-8- (3,5-bis-trifluoromethyl-benzoyl) -3- (2-methylsulfanyl-ethyl) -1,4,8-triaza-spiro [4.5] decan-2-one 462 8- (3-Cyclopentyl-propionyl) -3- (2-methylsulfanyl-ethyl) -1- (2-nitro-benzyl) -1,4,8-triaza-spiro [4.5] decan-2-one 465 1- (3,5-dimethyl-benzyl) -3-isobutyl-8- (4-nitro-benzoyl) -1,4,8-triaza-spiro [4.5] decan-2-one 466 8- (3-Cyclopentyl-propionyl) -1- (3,5-dimethyl-benzyl) -3-isobutyl-1,4,8-triaza-spiro [4.5] decan-2-one 467 3- [3-Isopropyl-8- (isoxazole-5-carbonyl) -2-oxo-1,4,8-triaza-spiro [4.5] dec-1-ylmethyl] -benzonitrile 468 3-benzyl-1- (2-fluoro-benzyl) -8- (2-methyl-6-trifluoromethyl-pyridin-3-carbonyl) -1,4,8-triaza-spiro [4.5] decan-2-one

Pharmakologische Daten:Pharmacological data:

Die Affinität der erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der allgemeinen Formel I zum humanen µ-Opioidrezeptor, deren Affinität zur Batrachotoxin-(BTX)-Bindungsstelle des Natriumkanals sowie die Hemmung der Noradrenalin- bzw. 5-HT-Wiederaufnahme, wurde wie vorstehend beschrieben bestimmt. Des weiteren wurde - ebenfalls wie vorstehend beschrieben - die analgetische Wirksamkeit der erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der allgemeinen Formel I im Writhing-Test an der Maus bestimmt.The affinity of the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds according to the invention of the general formula I for the human μ-opioid receptor, their affinity for the batrachotoxin (BTX) binding site of the sodium channel and the inhibition of noradrenaline or 5-HT reuptake, was determined as described above. Furthermore, the analgesic activity of the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I according to the invention in the writhing test on the mouse was also determined as described above.

Die erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der vorstehend angegebenen allgemeinen Formel I zeigen eine gute bis sehr gute Inhibierung der Noradrenalin-Wiederaufnahme sowie eine gute bis sehr gute Inhibierung der 5-Hydroxy-Tryptophan-Wiederaufnahme. Im Writhing-Test an der Maus zeigen die erfindungsgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen der allgemeinen Formel I eine ausgeprägte analgetische Wirksamkeit.The substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the above-indicated general formula I according to the invention exhibit good to very good inhibition of norepinephrine reuptake and good to very good inhibition of 5-hydroxytryptophan resumption. In the writhing test on the mouse, the substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds of the general formula I according to the invention exhibit pronounced analgesic activity.

Darüber hinaus zeigen diese erfindungsgemäßen Verbindungen auch ausgezeichnete Affinitäten für Opioid-Rezeptoren, insbesondere für den µ-Opioid-Rezeptor und/oder für die Batrachotoxin-(BTX)-Bindungsstelle des Natriumkanals.In addition, these compounds of the invention also show excellent affinities for opioid receptors, in particular for the μ-opioid receptor and / or for the batrachotoxin (BTX) binding site of the sodium channel.

In den nachfolgenden Tabellen I und II sind die jeweiligen pharmakologischen Daten für die beispielgemäßen substituierten 1,4,8-Triazaspiro[4.5]decan-2-on-Verbindungen wiedergegeben. Tabelle I: Beispiel %Hemmung der Writhingreaktion Nr. (Dosierung in mg/kg intravenös) 25 42 (10) 31 36 (10) 55 45 (10) 53 30 (10) 2 51 (10) Tabelle II: Beispiel BTX Inhibition µ (Naloxon), 1µM, % Hemmung Uptake 5-HT, Ratte, 1µM,% Hemmung 25 47 66 66 29 60 38 45 31 61 34 30 35 42 29 65 80 28 47 27 79 78 38 87 94 33 49 10 53 94 62 48 87 61 41 60 39 80 59 49 53 58 46 46 57 44 60 72 56 67 55 64 54 37 81 53 48 Tabelle III: Beispiel BTX Inhibierung Uptake_5-HT, Ratte, 1µM, % Hemmung Uptake (NA), Ratte, 10µM,% Hemmung 67 46 68 75 71 53 52 72 39 74 47 78 56 33 80 30 81 43 84 64 86 50 38 87 56 88 34 32 89 43 41 90 41 35 92 30 30 94 38 95 31 97 67 30 98 57 36 99 66 79 42 100 42 32 101 78 33 103 34 30 104 41 48 36 105 66 68 108 37 109 50 32 110 33 111 42 58 38 112 43 42 113 35 46 114 53 115 30 34 116 37 34 118 44 38 30 120 32 121 41 37 122 34 38 123 36 125 44 36 126 34 44 129 30 47 130 32 131 37 132 54 133 35 135 31 137 59 138 30 139 31 141 45 36 142 32 143 42 144 51 145 64 89 147 45 148 43 32 149 33 33 150 56 72 152 56 153 63 155 74 156 60 157 64 159 40 161 39 163 71 165 63 166 47 167 38 52 168 44 46 169 51 170 46 171 62 172 49 76 175 38 69 176 30 37 177 30 79 178 49 179 46 180 42 63 181 43 184 62 186 32 187 47 188 69 70 189 40 190 43 191 30 192 53 194 32 195 34 50 196 52 197 41 198 30 200 44 45 201 42 202 56 203 48 34 204 44 42 206 55 207 57 76 208 33 209 67 69 210 51 31 213 43 215 32 216 55 218 39 57 219 30 220 62 221 36 79 222 60 223 62 49 224 30 225 55 32 228 32 229 36 230 30 72 231 31 233 30 234 45 236 50 48 237 42 63 238 31 239 36 240 30 54 241 58 242 42 243 46 244 51 245 60 247 32 248 249 34 55 251 50 252 73 253 82 254 34 255 44 256 48 94 57 257 35 59 258 32 259 50 261 39 262 70 60 263 50 264 63 36 265 34 32 266 57 94 38 268 31 269 40 270 33 31 37 271 44 31 272 31 273 51 38 274 85 97 64 275 61 33 276 95 46 277 43 278 39 56 279 60 48 280 30 60 35 281 56 30 282 49 283 51 284 51 285 32 65 286 47 287 32 41 41 288 32 45 290 30 31 291 33 38 292 40 40 293 31 55 294 33 53 295 63 36 296 36 30 297 36 32 298 48 34 30 299 36 66 300 33 302 39 303 30 304 33 34 37 305 51 37 306 68 85 307 31 308 59 309 82 43 310 48 311 49 313 60 315 61 317 62 33 319 70 320 38 322 36 323 43 33 324 62 31 325 32 326 68 328 32 33 329 43 55 330 31 45 331 46 58 38 332 36 In the following Tables I and II, the respective pharmacological data for the exemplary substituted 1,4,8-triazaspiro [4.5] decan-2-one compounds are given. <b> Table I: </ b> example % Inhibition of the writhing reaction No. (Dosage in mg / kg intravenously) 25 42 (10) 31 36 (10) 55 45 (10) 53 30 (10) 2 51 (10) example BTX inhibition μ (naloxone), 1 μM,% inhibition Uptake 5-HT, rat, 1μM,% inhibition 25 47 66 66 29 60 38 45 31 61 34 30 35 42 29 65 80 28 47 27 79 78 38 87 94 33 49 10 53 94 62 48 87 61 41 60 39 80 59 49 53 58 46 46 57 44 60 72 56 67 55 64 54 37 81 53 48 example BTX inhibition Uptake_5-HT, rat, 1μM,% inhibition Uptake (NA), rat, 10μM,% inhibition 67 46 68 75 71 53 52 72 39 74 47 78 56 33 80 30 81 43 84 64 86 50 38 87 56 88 34 32 89 43 41 90 41 35 92 30 30 94 38 95 31 97 67 30 98 57 36 99 66 79 42 100 42 32 101 78 33 103 34 30 104 41 48 36 105 66 68 108 37 109 50 32 110 33 111 42 58 38 112 43 42 113 35 46 114 53 115 30 34 116 37 34 118 44 38 30 120 32 121 41 37 122 34 38 123 36 125 44 36 126 34 44 129 30 47 130 32 131 37 132 54 133 35 135 31 137 59 138 30 139 31 141 45 36 142 32 143 42 144 51 145 64 89 147 45 148 43 32 149 33 33 150 56 72 152 56 153 63 155 74 156 60 157 64 159 40 161 39 163 71 165 63 166 47 167 38 52 168 44 46 169 51 170 46 171 62 172 49 76 175 38 69 176 30 37 177 30 79 178 49 179 46 180 42 63 181 43 184 62 186 32 187 47 188 69 70 189 40 190 43 191 30 192 53 194 32 195 34 50 196 52 197 41 198 30 200 44 45 201 42 202 56 203 48 34 204 44 42 206 55 207 57 76 208 33 209 67 69 210 51 31 213 43 215 32 216 55 218 39 57 219 30 220 62 221 36 79 222 60 223 62 49 224 30 225 55 32 228 32 229 36 230 30 72 231 31 233 30 234 45 236 50 48 237 42 63 238 31 239 36 240 30 54 241 58 242 42 243 46 244 51 245 60 247 32 248 249 34 55 251 50 252 73 253 82 254 34 255 44 256 48 94 57 257 35 59 258 32 259 50 261 39 262 70 60 263 50 264 63 36 265 34 32 266 57 94 38 268 31 269 40 270 33 31 37 271 44 31 272 31 273 51 38 274 85 97 64 275 61 33 276 95 46 277 43 278 39 56 279 60 48 280 30 60 35 281 56 30 282 49 283 51 284 51 285 32 65 286 47 287 32 41 41 288 32 45 290 30 31 291 33 38 292 40 40 293 31 55 294 33 53 295 63 36 296 36 30 297 36 32 298 48 34 30 299 36 66 300 33 302 39 303 30 304 33 34 37 305 51 37 306 68 85 307 31 308 59 309 82 43 310 48 311 49 313 60 315 61 317 62 33 319 70 320 38 322 36 323 43 33 324 62 31 325 32 326 68 328 32 33 329 43 55 330 31 45 331 46 58 38 332 36

Claims (32)

  1. Substituted 1,4,8-triazaspiro[4.5]decan-2-one compounds of the general formula I,
    Figure imgb0027
     in which
    R1 stands for a hydrogen residue, or for a linear or branched unsubstituted alkyl residue optionally comprising at least one heteroatom as link, or for a linear or branched, unsubstituted or at least monosubstituted alkenyl residue optionally comprising at least one heteroatom as link, or for a linear or branched, unsubstituted or at least monosubstituted alkynyl residue optionally comprising at least one heteroatom as link, or for an unsubstituted or at least monosubstituted aryl residue or heteroaryl residue, which is attached via a linear or branched alkylene group optionally comprising at least one heteroatom as link, or for a -C(=O)-OR5 residue attached via a linear or branched alkylene group or for an -O-(C=O)-R6 residue attached via a linear or branched alkylene group,
    R2 stands for a hydrogen residue, or for a linear or branched, unsubstituted or at least monosubstituted alkyl residue optionally comprising at least one heteroatom as link, or for a linear or branched, unsubstituted or at least monosubstituted alkenyl residue optionally comprising at least one heteroatom as link, or for a linear or branched, unsubstituted or at least monosubstituted alkynyl residue optionally comprising at least one heteroatom as link, or for an unsubstituted or at least monosubstituted aryl residue or heteroaryl residue, which can be attached via a linear or branched alkylene group optionally comprising at least one heteroatom as link,
    R3 stands for a hydrogen residue, or for a linear or branched unsubstituted or at least monosubstituted alkyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted alkenyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted alkynyl residue optionally comprising at least one heteroatom as link, or for an unsubstituted or at least monosubstituted aryl residue or heteroaryl residue, which is attached via a linear or branched unsubstituted or at least monosubstituted alkylene group optionally comprising at least one heteroatom as link and optionally fused with an unsubstituted or at least monosubstituted monocyclic ring system, or for an unsubstituted or at least monosubstituted cycloaliphatic residue optionally comprising at least one heteroatom as ring member and optionally attached via a linear or branched unsubstituted or at least monosubstituted alkylene group optionally comprising at least one heteroatom as link, which can be bridged by a linear or branched unsubstituted or at least monosubstituted alkylene group optionally comprising at least one heteroatom as link and/or fused with an unsubstituted or at least monosubstituted monocyclic ring system, or for a -C(=O)-R4 group,
    R4 stands for a linear or branched unsubstituted or at least monosubstituted alkyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted alkenyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted alkynyl residue optionally comprising at least one heteroatom as link,
    or for an unsubstituted or at least monosubstituted aryl residue or heteroaryl residue, which residue can be attached via a linear or branched unsubstituted or at least monosubstituted alkylene group, alkenylene group, or alkynylene group, which groups optionally comprise at least one heteroatom as link, and/or can be fused with an unsubstituted or at least monosubstituted monocyclic ring system,
    or for an unsubstituted or at least monosubstituted cycloaliphatic residue optionally comprising at least one heteroatom as ring member and optionally attached via a linear or branched unsubstituted or at least monosubstituted alkylene group optionally comprising at least one heteroatom as link, which cycloaliphatic residue can be at least singly bridged by a linear or branched unsubstituted or at least monosubstituted alkylene group and/or fused with an unsubstituted or at least monosubstituted monocyclic ring system,
    or for a -C(=O)-OR7 residue attached via a linear or branched unsubstituted or at least monosubstituted alkylene group, or for an -O-(C=O)-R8 residue attached via a linear or branched unsubstituted or at least monosubstituted alkylene group or for a -(C=O)-R9 residue attached via a linear or branched unsubstituted or at least monosubstituted alkylene group,
    R5 and R6 each independently stand for a linear or branched alkyl residue, or for a linear or branched alkenyl residue or for a linear or branched alkynyl residue,
    R7 and R8 each independently stand for a hydrogen residue, or for a linear or branched alkyl residue, or for a linear or branched alkenyl residue, or for a linear or branched alkynyl residue, or for an unsubstituted or at least monosubstituted aryl residue or heteroaryl residue,
    R9 stands for a linear or branched alkyl residue, or for a linear or branched alkenyl residue or for a linear or branched alkynyl residue,
    in each case optionally in the form of one of the pure stereoisomers thereof, particularly enantiomers or diastereoisomers thereof, the racemates thereof or in the form of a mixture of stereoisomers thereof, particularly the enantiomers and/or diastereoisomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.
    in which "at least monosubstituted" in connection with an alkyl, alkenyl or alkynyl residue stands for a mono- or polysubstituted alkyl, alkenyl or alkynyl residue, the substituents being in each case mutually independently selected from the group consisting of F, Cl, Br, I, C1-6-alkoxy, -NO2, -OH, -SH, -(C=O)-OH, -(C=O)-O-C1-4-alkyl, -O-(C=O)-C1-4-alkyl, -CH2-O-CH2-phenyl, -CN, -CF3, -CHF2, -CH2F, unsubstituted phenyl and -NRaRb, in which Ra and Rb may in each case be mutually independently selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert.-butyl, -(C=O)-O-C1-4-alkyl, and unsubstituted phenyl;
    in which "at least monosubstituted" in connection with a cycloaliphatic residue stands for a mono- or polysubstituted cycloaliphatic residue, the substituents being in each case mutually independently selected from the group consisting of F, Cl, Br, C1-6-alkoxy, oxo, C1-6-alkyl, hydroxy, -CN, -CF3, -CHF2, -CH2F, unsubstituted phenyl, -NRaRb, in which Ra and Rb may in each case be mutually independently selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl and unsubstituted phenyl, thioxo (=S), I, -SF5, -NO2, -O-CF3, -S-CF3, -SH, -S-C1-5-alkyl, -C(=O)-H, -C(=O)-C1-5-alkyl, -C(=O)-OH, -C(=O)-O-C1-5-alkyl, -(CH2)-C(=O)-OH, -CH2-C(=O)-O-C1-5-alkyl, -(CH2)-benzo[b]furanyl, -O-phenyl, - O-benzyl, phenyl, benzyl, naphthyl and -(CH2)-naphthyl, wherein the cyclic moiety of the residues -0-phenyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, benzyl, naphthyl and -(CH2)-naphthyl can in each case be substituted with 1, 2, 3, 4 or 5 substituents mutually independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-C1-5-alkyl, -C1-5-alkyl, -O-CF3, -S-CF3, phenyl and -O-benzyl;
    in which "at least monosubstituted" in connection with an aryl or heteroaryl residue stands for a mono- or polysubstituted aryl or heteroaryl residue, the substituents preferably being in each case mutually independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, C1-5-alkyl, OH, SH, C1-5-alkoxy, C1-5-perfluoroalkoxy, -C(=O)-C1-5-alkyl, -C(=O)-O-C1-5-alkyl, -(CH2)1-3-O-(C=O)-phenyl, -S-C1-5-alkyl, -S(=O)2-C1-6-alkyl, -S(=O)2-NH2, -NH,-(C=O)-CH3, -S-CHF2, -S-CH2F, -C(=O)-C1-5-perfluoroalkyl, -CF3, -CHF2, -CH2F, phenyl, phenoxy and -NRaRb, in which Ra and Rb may be in each case mutually independently selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl and unsubstituted phenyl, -SF5, -O-C2-5-Alkenyl, -O-CF3, -O-CHF2, -O-CH2F, -C(=O)-OH, -O-C(=O)-C1-5-alkyl, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-C1-5-alkyl, -NH-C1-5 alkyl, -N(C1-5-alkyl)2, -NH-C(=O)-O-C1-5-alkyl, -C(=O)-H, -C(=O)-C1-5-alkyl, -C(=O)-NH2, -C(=O)-NH-C1-5-Alkyl, C(=O)-N-(C1-5-alkyl)2, -S(=O)2-NH-C1-5 alkyl, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, wherein the cyclic moiety of the residues -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl and benzyl can be substituted with 1, 2, 3, 4 or 5 substituents mutually independently selected from the group consisting of F, Cl, Br, -OH, - CF3, -SF5, -CN, -NO2, -O-C1-5-alkyl, -C1-5-alkyl, -O-CF3, -S-CF3, phenyl and -O-benzyl and the phenyl and phenoxy substituents can themselves be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -S-CHF2, -CF3, -CHF2, -CH2F, -CN, -NO2, C1-5-alkyl and C1-5-alkoxy;
    in which "at least monosubstituted" in connection with a monocyclic ring system stands for a mono- or polysubstituted monocyclic ring system, the substituents preferably being in each case mutually independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, oxo, C1-5-alkyl, C1-5-alkoxy, C1-5-perfluoroalkoxy, -C(=O)-C1-5-alkyl, -C(=O)-O-C1-5-alkyl, -S(=O)2-C1-6-alkyl -C(=O)- C1-5-perfluoroalkyl, -CF3, CHF2, CH2F, and -NRaRb, in which Ra and Rb may be in each case mutually independently selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl and unsubstituted phenyl, thioxo (=S), -SF5, -OH, -O-C2-5-alkenyl, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-C1-5-alkyl, -C(-O)-OH, -O-C(=O)-C1-5-alkyl, -O-C(=O)-phenyl,-(CH2)-O-C(=O)-C1-5-alkyl, -(CH2)-O-C(=O)-phenyl, -NH-C1-5 alkyl, -N(C1-5-alkyl)2, -NH-C(=O)-O-C1-5-alkyl, -NH-C(=O)-C1-5-alkyl, -C(=O)-H, -C(=O)-NH2, -C(=O)-NH-C1-5-alkyl, C(=O)-N-(C1-5-alkyl)2, - S(=O)2-NH2, -S(=O)2-NH-C1-5-alkyl, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, wherein the cyclic moiety of the residues -O-C(=O)-phenyl, - (CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, - (CH2)-benzo[b]furanyl and benzyl can in each case be substituted with 1, 2, 3, 4 or 5 substituents mutually independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, - O-C1-5-alkyl, -C1-5-alkyl, -O-CF3, -S-CF3, phenyl and -O-benzyl;
    in which "at least monosubstituted" in connection with a linear or branched alkylene, alkenylene or alkynylene group stands for a mono- or polysubstituted linear or branched, alkylene, alkenylene or alkynylene group, the substituents preferably being in each case mutually independently selected from the group consisting of F, Cl, Br, C1-6-alkoxy, hydroxy, CN, CF3, CHF2, CH2F, unsubstituted phenyl and -NaRb, in which Ra and Rb may be in each case mutually independently selected from the group consisting of H, C1-3-alkyl and unsubstituted phenyl;
    excluding those compounds of the general formula I in which
    A)
    R1 stands for a hydrogen residue, a C1-6-alkyl residue, a C1-6-alkoxy residue, a C2-6-alkenyl residue, a C2-6-alkynyl residue or for a C1-6-alkyl residue that is monosubstituted with a phenyl residue,
    R2 stands for a hydrogen residue, a C1-6-alkyl residue, a C1-6-alkoxy residue, a C2-6-hydroxyalkyl residue, a C2-6-alkenyl residue, a C2-6-alkynyl residue, a phenyl residue, a C1-6-alkyl residue monosubstituted, disubstituted, or trisubstituted with a phenyl residue, an -O-C1-6-alkanoyl residue, an -O-C1-6-alkyl residue, an -O-C2-6-hydroxyalkyl residue, a -O-C2-6-alkenyl residue, an -O-C2-6-alkynyl residue or for an -O-C1-6-alkyl residue that is monosubstituted, disubstituted, or trisubstituted with a phenyl residue,
    R3 stands for a hydrogen residue, a C1-6-alkyl residue, a C2-6-alkenyl residue, a C2-6-alkynyl residue, a C3-7-cycloalkyl residue, a C1-6-alkyl residue that is substituted with 1 to 6 halogen atoms, a hydroxy-C1-6-alkyl residue, a C1-6-alkoxy residue, a C1-6-alkylthio residue, a C1-6-alkoxy-C1-6-alkyl residue, a carboxy-C1-6-alkyl residue, a (C1-6-alkoxy)carbonyl-C1-6-alkyl residue, an amino-C1-6-alkyl residue, a mono-(C1-6-alkyl)- amino-C1-6-alkyl residue, a di(C1-6-alkyl)-amino-C1-6-alkyl residue, a 2-oxo-pyrrolidin-1-ylmethyl residue, an aryl residue, a diarylmethylol residue, a C1-6-alkyl residue that is substituted with one or two aryl residues, a C1-6-alkanoyl residue, or an arylcarbonyl residue, aryl in each case standing for an unsubstituted phenyl residue or for a phenyl residue which is substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-6-alkyl, C1-6-alkoxy, and CF3,
    and the physiologically compatible salts thereof, enantiomers thereof and racemates thereof,
    and
    B)
    the residues R1, R2, and R3 in each case stand for a hydrogen residue or a hydrocarbon residue and in each case the salts thereof.
  2. Compounds according to claim 1, characterized in that R1 stands for a hydrogen residue, or for a linear or branched unsubstituted, C1-10-alkyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted C2-10-alkenyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted C2-10-alkynyl residue optionally comprising at least one heteroatom as link, or for an unsubstituted or at least monosubstituted five-membered to fourteen-membered aryl residue or heteroaryl residue, which is attached via a linear or branched C1-5-alkylene group optionally comprising at least one heteroatom as link, or for a -C(=O)-OR5 residue attached via a linear or branched C1-5 alkylene group, or for a -O-C(=O)-R6 residue attached via a linear or branched C1-5 alkylene group,
    preferably for a hydrogen residue, or for a linear or branched, unsubstituted C1-5-alkyl residue, or for a linear or branched, unsubstituted C2-5-alkenyl residue, or for a linear or branched, unsubstituted C2-5-alkynyl residue, or for an unsubstituted or at least monosubstituted phenyl or naphthyl residue attached via a linear or branched C1-5-alkylene group, optionally comprising one or more oxygen atoms as links, or for a -C(=O)-OR5 residue attached via a linear or branched C1-4-alkylene group or for a -O-C(=O)-R6 residue attached via a linear or branched C1-4-alkylene group,
    particularly preferably for a hydrogen residue, or for a linear or branched unsubstituted C1-4-alkyl residue, or for a linear or branched unsubstituted C2-5-alkenyl residue, or for a linear or branched unsubstituted C2-3-alkynyl residue, or for a phenyl or naphthyl residue, which is attached via a -(CH2) bridge, -(CH2)2 bridge, -(CH2)3 bridge or -(CH2)2-O- bridge and is optionally monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -CN, -NO2, C1-5-alkyl, C1-5-alkoxy, -C(=O)-C1-5-alkyl, -C(=O)-O-C1-5-alkyl, -S(=O)2C-1-6-alkyl, - C(=O)-C1-5 perfluoroalkyl, -CF3, CHF2, and CH2F, or for a -C(=O)-OR5 residue attached via a -(CH2) group or for a -O-C(=O)-R6 residue attached via a -(CH2) group, -(CH2)2 group, -(CH2)3 group or - (CH2)4 group.
  3. Compounds according to claim 1 or claim 2, characterized in that R2 stands for a hydrogen residue, or for a linear or branched unsubstituted or at least monosubstituted C1-10-alkyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted C2-10-alkenyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted C2-10-alkynyl residue optionally comprising at least one heteroatom as link, or for an unsubstituted or at least monosubstituted, five- to fourteen-membered aryl residue or heteroaryl residue, which can be attached via a linear or branched C1-5-alkylene group optionally comprising at least one heteroatom as link,
    preferably for a hydrogen residue, or for a linear or branched, unsubstituted C1-5 alkyl residue, optionally comprising one or more oxygen atoms and/or one or more sulfur atoms as link(s) or for a phenyl or naphthyl residue which is monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -CN, -NO2, C1-5-alkyl, C1-5-alkoxy, -C(=O)-C1-5-alkyl, -C(=O)-O-C1-5-alkyl, -S(=O)2-C1-6-alkyl, -C(=O)-C1-5-perfluoroalkyl, -CF3, -CHF2, and -CH2F and/or can be attached via a -(-CH2)- bridge, a -(CH2)2- bridge, a -(CH2)3- bridge, or a -(CH2)2-O-bridge,
    particularly preferably for a hydrogen residue, or for a linear or branched unsubstituted C1-5 alkyl residue optionally comprising one or more sulfur atoms as links or for a phenyl residue, wherein the phenyl residue can be monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -CN, -NO2, C1-5-alkyl, C1-5-alkoxy, -C(=O)-C1-5-alkyl, - C(=O)-O-C1-5-alkyl, -S(=O)2-C1-6-alkyl, -C(=O)- C1-5-perfluoroalkyl, -CF3, -CHF2, and -CH2F and/or can be attached via a -(CH2)- bridge.
  4. Compounds according to one or more of claims 1-3, characterized in that R3 stands for a hydrogen residue, or for a linear or branched unsubstituted or at least monosubstituted C1-10-alkyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted C2-10-alkenyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted C2-10alkynyl residue optionally comprising at least one heteroatom as link, or for an unsubstituted or at least monosubstituted five-membered to fourteen-membered aryl residue or heteroaryl residue, which is attached via a linear or branched unsubstituted or at least monosubstituted C1-5-alkylene group optionally comprising at least one heteroatom as link and is optionally fused with an unsubstituted or at least monosubstituted monocyclic ring system, or for an unsubstituted or at least monosubstituted C3-8-cycloaliphatic residue, optionally comprising at least one heteroatom as ring member and which can be attached via a linear or branched unsubstituted or at least monosubstituted C1-5 alkylene group optionally comprising at least one heteroatom as link and/or can be fused with an unsubstituted or at least monosubstituted monocyclic ring system, or for a -C(=O)-R4 group,
    preferably for a hydrogen residue, or for a biphenyl residue, which is attached via a -(CH2)- bridge, a - (CH2)2- bridge or a -(CH2)3- bridge, or for a C(=O)-R4 group,
    particularly preferably for a -C(=O)-R4 group,
  5. Compounds according to one or more of claims 1 to 4, characterized in that R4
    stands for a linear or branched unsubstituted or at least monosubstituted C1-10-alkyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted C2-10-alkenyl residue optionally comprising at least one heteroatom as link, or for a linear or branched unsubstituted or at least monosubstituted C2-10-alkynyl residue optionally comprising at least one heteroatom as link,
    or for an unsubstituted or at least monosubstituted five-membered to fourteen-membered aryl residue or heteroaryl residue, which can be attached via a linear or branched unsubstituted or at least monosubstituted C1-5-alkylene group, C2-5-alkenylene group, or C2-5-alkynylene group optionally comprising at least one heteroatom as link and/or can be fused with an unsubstituted or at least monosubstituted monocyclic ring system,
    or for an unsubstituted or at least monosubstituted C3-8 cycloaliphatic residue optionally comprising at least one heteroatom as ring member and optionally attached via a linear or branched unsubstituted or at least monosubstituted C1-6 alkylene group optionally comprising at least one heteroatom as link, which cycloaliphatic residue can be at least singly bridged by a linear or branched unsubstituted or at least monosubstituted C1-6-alkylene group and/or fused with an unsubstituted or at least monosubstituted monocyclic ring system,
    or for a -C(=O)-OR7 residue attached via a linear or branched unsubstituted or at least monosubstituted C1-5-alkylene group, or for an -O-(C=O)-R8 residue attached via a linear or branched unsubstituted or at least monosubstituted C1-5-alkylene group or for a -(C=O)-R9 residue attached via a linear or branched unsubstituted or at least monosubstituted C1-5 alkylene group,
    preferably for a linear or branched C1-10-alkyl residue optionally comprising one or more oxygen atoms and/or one or more sulfur atoms as link(s), which residue can be unsubstituted or at least monosubstituted, identically or differently, with a substituent selected from the group consisting of phenyl, di-(C1-5 alkylamino), carboxy, and -NH-(C=O)-O-C1-5-alkyl, or for a linear or branched C2-5-alkenyl residue, or for a phenyl residue, naphthyl residue, furyl (furanyl) residue, thienyl (thiophenyl) residue or [1,2,3]-triazolyl residue, benzo[1.3]dioxolyl residue, benzo[1,2,5]oxadiazolyl residue, chromanyl residue, pyrimidinyl residue, pyrazolyl residue, pyridinyl residue, isoxazolyl residue, or [1,2,3]-thiadiazolyl residue, wherein the cyclic residue may in each case be attached via over a-(CH2)-, -(CH2)-O- bridge, a -CH=CH- bridge, a -(CH2)2- bridge, a -(CH2)2-O- bridge or a -(CH2)3-bridge and/or can be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I, -CN, -NO2, C1-5-alkyl, C1-5-alkoxy, C1-5-perfluoroalkoxy, - C(=O)-C1-5-alkyl, -C(=O)-O-C1-5-alkyl, -(CH2)1-3-O-C(=O)-phenyl, -N(CH3)2, -S(=O)2-C1-6-alkyl, -S(=O)2-NH2, -C(=O)-C1-5-perfluoroalkyl, -S-C1-5-alkyl, -S-CH2F, -S-CHF2, -SCF3, -CF3, -NH-(C=O)-CH3, -CHF2, -CH2F, phenyl, and phenoxy, wherein the latter phenyl and phenoxy substituents can themselves be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -S-CHF2, -CF3, -CHF2, -CH2F, CN, NO2, C1-5-alkyl, and C1-5-alkoxy,
    or for a three-membered, four-membered, five-membered, six-membered, seven-membered, or eight-membered cycloaliphatic residue optionally comprising at least one heteroatom as ring member and optionally attached via a -(CH2)- bridge, a -(CH2)2- bridge, or a -(CH2)3- bridge, which cycloaliphatic residue is at least singly bridged at least by one -(C(CH3)2)- or -(CH2) group and/or unsubstituted or monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of C1-5-alkyl, C1-5-alkoxy, -CF3, -CHF2, -CH2F, and oxo,
    or for a -C(=O)-OR7 residue attached via a linear or branched unsubstituted or at least monosubstituted C1-5 alkylene group, or for a -O-(C=O)-R8 residue attached via a linear or branched unsubstituted or at least monosubstituted C1-5 alkylene group, or for a -(C=O)-R9 residue attached via a linear or branched unsubstituted or at least monosubstituted C1-5 alkylene group,
    particularly preferably for a linear or branched C1-8-alkyl residue optionally comprising one or more oxygen atoms and/or one or more sulfur atoms as links, which residue can be unsubstituted or at least monosubstituted, identically or differently, with a substituent selected from the group consisting of unsubstituted phenyl, dimethylamino, carboxy, and -NH-(C=O)-O-C(CH3)3, or for a linear or branched unsubstituted C2-4-alkenyl residue, or for a phenyl residue, naphthyl residue, furyl-(furanyl) residue, thienyl-(thiophenyl) residue, [1,2,3]-triazolyl residue, chromanyl residue, benzo[1.3]dioxolyl residue, benzo[1,2,5]oxadiazoleyl residue, pyrimidinyl residue, pyrazolyl residue, pyridinyl residue, isoxazolyl residue, or [1,2,3]-thiadiazolyl residue, wherein the cyclic residue can in each case be attached via a - (CH2)- bridge, a -(CH2)-O- bridge, a -CH=CH- bridge, a -(CH2)2- bridge, a -(CH2)2-O- bridge, or a-(CH2)3-bridge and/or can be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I, methyl, ethyl, isopropyl, n-propyl, sec-butyl, tert.-butyl, n-butyl, methoxy, ethoxy, -CF3, -OCF3, -CH2-O-C(=O)-phenyl, -NO2, -S-CF3, -S-CHF2, -N(CH3)2, -NH-CO-CH3, -CN, -SO2-NH2, phenyl, and phenoxy, wherein the latter phenyl and phenoxy substituents can themselves be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -CH3, and -OCH3,
    or for a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolidine, 4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptyl residue or adamantyl residue optionally attached via a -(CH2)- bridge, a -(CH2)2-bridge, or a -(CH2)3- bridge, and which is unsubstituted or monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of C1-5-alkyl, C1-5-alkoxy, -CF3, -CHF2, -CH2F, and oxo,
    or for a -C(=O)-OR7 residue attached via a -(CH2)- group, a -(CH2)2 group, a -C(H)-phenyl group, or a -C(CH3)2 group, or for a -O-(C=O)-R8 residue attached via a -(CH2)- group, a -(CH2)2 group, a -C(H)-phenyl group, or a -C(CH3)2 group, or for a -(C=O)-R9 residue attached via a -(CH2)- group or a - (CH2)2 group,
    very particularly preferably for a linear or branched C6-8-alkyl residue optionally comprising one or more oxygen atoms and/or one or more sulfur atoms as links, which can be unsubstituted or at least monosubstituted, identically or differently, with a substituent selected from the group consisting of unsubstituted phenyl, dimethylamino, carboxy, and -NH-(C=O)-O-C(CH3)3, or for a linear or branched unsubstituted C2-4 alkenyl residue, or for a naphthyl residue, furyl-(furanyl) residue, thienyl-(thiophenyl) residue, [1,2,3]-triazolyl residue, chromanyl residue, benzo[1.3]dioxolyl residue, benzo[1,2,5]oxadiazolyl residue, pyrimidinyl residue, pyrazolyl residue, pyridinyl residue, isoxazolyl residue, or [1,2,3]-thiadiazolyl residue, wherein the cyclic residue can in each case be attached via a - (CH2)- bridge, a -(CH2)-O- bridge, a -CH=CH- bridge, a -(CH2)2- bridge, a -(CH2)2-O- bridge, or a - (CH2)3 bridge and/or can be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, I, methyl, ethyl, isopropyl, n-propyl, sec-butyl, tert.-butyl, n-butyl, methoxy, ethoxy, -CF3, -OCF3, -CH2-O-C(=O)-phenyl, -NO2, -S-CF3, -S-CHF2, -N(CH3)2, -NH-CO-CH3, -CN, -SO2-NH2, phenyl, and phenoxy, wherein the latter phenyl and phenoxy substituents can themselves be mono- or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, CH3, and OCH3, or for 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-CF3-S-phenyl, 3-CF3-S-phenyl, 4-CF3-S-phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-CHF2-S-phenyl, 3-CHF2-S-phenyl, 4-CHF2-S-phenyl, 2-dimethylaminophenyl, 3-dimethylaminophenyl, 4-dimethylaminophenyl, 2-phenyl-(C=O)-O-CH2-phenyl, 3-phenyl-(C=O)-O-CH2-phenyl, 4-phenyl-(C=O)-O-CH2-phenyl, 2-CH3-(C=O)-NH-phenyl, 3-CH3-(C=O)-NH-phenyl, 4-CH3-(C=O)-NH-phenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl, 2-NH2-SO2-phenyl, 3-NH2-SO2-phenyl, 4-NH2-SO2-phenyl, pentafluorophenyl, 4-methyl-3-nitrophenyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, -CH=CH-phenyl, wherein the phenyl residue can be mono- or polysubstituted in the 2, 3 or 4 position, identically or differently, with a residue selected from the group consisting of F, Cl, Br, and CF3, -CH2-O-phenyl, wherein the phenyl residue can be mono- or polysubstituted in 2, 3 or 4 position, identically or differently, with a residue selected from the group consisting of F, Cl, Br, and CF3, for a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, imidazolidine, 4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptyl residue or adamantyl residue, which residues are optionally attached via a -(CH2)- bridge, a -(CHF2)2- bridge, or a -(CH2)3- bridge, wherein the cyclic residues can in each case be unsubstituted or monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of C1-5 alkyl, C1-5 alkoxy, -CF3, CHF2, CH2F, and oxo, for a -C(=O)-OR7 residue attached via a -(CH2) group, -(CH2)2 group, -C(H)(phenyl) group, or -C(CH3)2 group, for a -O-(C=O)-R8 residue attached via a -(CH2) group, -(CH2)2 group, - C(H)(phenyl) group, or -C(CH3)2 group, or for a -(C=O)-R9 residue attached via a -(CH2) group or a - (CH2)2 group.
  6. Compounds according to one or more of claims 1 to 5, characterized in that the residues R5 and R6 in each case mutually independently stand for a linear or branched C1-5-alkyl residue, a linear or branched C2-5-alkenyl residue or a linear or branched C2-5-alkynyl residue and preferably for a methyl residue, ethyl residue, n-propyl residue, or isopropyl residue.
  7. Compounds according to one or more of claims 1 to 6, characterized in that the residues R7 and R8 in each case mutually independently stand for a hydrogen residue, or for a linear or branched C1-5-alkyl residue, a linear or branched C2-5-alkenyl residue, a linear or branched C2-5-alkynyl residue, or for an optionally at least monosubstituted phenyl or naphthyl residue, preferably for a methyl residue, ethyl residue, n-propyl residue, or isopropyl residue, or for an unsubstituted phenyl residue.
  8. Compounds according to one or more of claims 1 to 7, characterized in that the residue R9 stands for a linear or branched C1-5-alkyl residue, a linear or branched C2-5-alkenyl residue, a linear or branched C2-5-alkynyl residue, preferably for a methyl residue, ethyl residue, n-propyl residue or isopropyl residue.
  9. Compounds according to one or more of claims 1 to 8, characterized in that
    R1 stands for a hydrogen residue, or for a linear or branched unsubstituted C1-4-alkyl residue, or for a linear or branched unsubstituted C2-5-alkenyl residue, or for a linear or branched unsubstituted C2-3-alkynyl residue, or for a phenyl or naphthyl residue, which is unsubstituted or monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -CN, -NO2, C1-5-alkyl, C1-5-alkoxy, -C(=O)-C1-5-alkyl, -C(=O)-O-C1-5-alkyl, -S(=O)2-C12-alkyl,-C(=O)-C1-5-perfluoroalkyl, -CF3, -CHF2, and -CH2F and/or is attached via a -(CH2)- bridge, a -(CH2)2-bridge, a -(CH2)3- bridge or a -(CHF2)2-O- bridge, or for a -C(=O)-OR5 residue attached via a -(CH2) group or for a -O-C(=O)-R6 residue attached via a -(CH2) group, a -(CH2)2 group, a -(CH2)3 group, or - (CH2)4 group,
    R2 stands for a hydrogen residue, or for a linear or branched unsubstituted C1-5-alkyl residue optionally comprising one or more sulfur atoms as link(s) or for a phenyl residue, wherein the phenyl residue can be monosubstituted or polysubstituted, identically or differently, with a substituent selected from the group consisting of F, Cl, Br, -CN, -NO2, C1-5-alkyl, C1-5-alkoxy, -C(=O)-C1-5-alkyl, -C(=O)-O-C1-5-alkyl, - S(=O)2-C1-6-alkyl, -C(=O)- C1-5-perfluoroalkyl, -CF3, -CHF2, and -CH2F, and/or can be attached via a - (CH2)- bridge,
    R3 stands for a hydrogen residue, or for a biphenyl residue, which is attached via a -(CH2)- bridge, a - (CH2)2- bridge, or a -(CH2)3- bridge, or for a C(=O)-R4 group,
    R4 stands for a residue, which is selected from the group consisting of methyl, ethyl, isopropyl, n-propyl, sec-butyl, isobutyl, tert.-butyl, n-butyl, n-pentyl, 1-methylbutyl, 2-dimethylpropyl, 1-ethylpropyl, 1-propylbutyl, 1-ethylpentyl, dimethylaminomethyl, -CH2-CH2-CH=CH2, -CH2-O-CH3, -CH2-O-CH2-CH2-O-CH3, -CH2-CH2-phenyl, -CH2-O-phenyl, -CH2-O-CH2-phenyl, -CH2-CH2-CH2-O-phenyl, - C(H)(phenyl)-(C2H5), -C(H)(CH3)-O-phenyl, -CH2-CH2-(C=O)-CH3, -CH2-O-(C=O)-CH3, -CH2-CH2-(C=O)-O-C2H5, -CH2-O-(C=O)-phenyl, -CH2-(C=O)-O-CH2-CH3, -C(H)(phenyl)-(C=O)-CH3, - C(H)(phenyl)-O-(C=O)-CH3, -C(CH3)2-O-(C=O)-CH3, -C(H)(NH-(C=O)-O-(CH3)3)-(CH2-O-CH2-phenyl), -C(CH3)2-CH2-COOH, unsubstituted phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-n-propylphenyl, 3-n-propylphenyl, 4-n-propylphenyl, 2-tert.-butylphenyl, 3-tert.-butylphenyl, 4-tert.-butylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-trifluoromethylphenyl, 3 trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-CF3-S-phenyl, 3-CF3-S-phenyl, 4-CF3-S-phenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2-CHF2-S-phenyl, 3-CHF2-S-phenyl, 4-CHF2-S-phenyl, 2-dimethylaminophenyl, 3-dimethylaminophenyl, 4-dimethylaminophenyl, 2-phenyl-(C=O)-O-CH2-phenyl, 3-phenyl-(C=O)-O-CH2-phenyl, 4-phenyl-(C=O)-O-CH2-phenyl, 2-CH3-(C=O)-NH-phenyl, 3-CH3-(C=O)-NH-phenyl, 4-CH3-(C=O)-NH-phenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl, 2-NH2-SO2-phenyl, 3-NH2-SO2-phenyl, 4-NH2-SO2-phenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,3-dimethylphenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 2,3-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, pentafluorophenyl, 2-chloro-6-fluorophenyl, 4-bromo-3-methylphenyl, 3-fluoro-4-methylphenyl, 3-chloro-2-fluorophenyl, 2-chloro-4-nitrophenyl, 5-fluoro-2-trifluoromethylphenyl, 3-fluoro-4-trifluoromethyl, 4-methyl-3-nitrophenyl, 2-chloro-5-trifluoromethyl, 2,5-bis-trifluoromethylphenyl, 3,5-bis-trifluoromethylphenyl, 2-chloro-6-fluoro-3-methylphenyl, 6-chloro-2-fluoro-3-methylphenyl, 2,6-difluoro-4-methylphenyl, 2,6-difluoro-3-methylphenyl, 3,4,5-trimethoxyphenyl, 2,3-difluoro-4-methylphenyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl, 4-bromobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, -CH=CH-phenyl, wherein the phenyl residue can be monosubstituted or polysubstituted in the 2, 3, or 4 position, identically or differently, with a residue selected from the group consisting of F, Cl, Br, and CF3, -CH2-O-phenyl, wherein the phenyl residue can be monosubstituted or polysubstituted in the 2, 3 or 4 position, identically or differently with a residue selected from the group consisting of F, Cl, Br, and CF3, 1-naphthyl, 2-naphthyl, 2-thienyl, 3-thienyl, 3-chlorothien-2-yl, 2-furanyl, 3-furanyl, 2,5-dimethylfuran-3-yl, 5-tert.-butyl-2-methylfuran-3-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 2-chloropyridin-4-yl, 6-chloropyridin-3-yl, 2-chloropyridin-3-yl, 2-ethylsulfanylpyridin-3-yl, 2-phenoxypyridin-3-yl, 2-methylsulfanylpyridin-3-yl, 2-methyl-6-trifluoromethylpyridin-3-yl, isoxazol-5-yl, 5-methylisoxazol-3-yl, 3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl, 3-(2-chlorophenyl)-5-methylisoxazol-4-yl, 3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl, 5-tert.-butyl-2-methyl-2H-pyrazol-3-yl, 1-phenyl-5-n-propyl-1H-pyrazol-4-yl, 1-(4-chlorophenyl)-5-trifluoromethyl-1H-pyrazol-4-yl, 2-tert.-butyl-5-methyl-2H-pyrazol-3-yl, 5-methyl-2-phenyl-2H-[1,2,3]triazol-4-yl, 4-methyl[1,2,3]thiadiazol-5-yl, 2-chloro-4-trifluoromethylpyrimidin-5-yl, 2-chloro-4-trifluoromethylpyrimidin-5-yl, benzo[1,2,5]oxadiazol-5-yl, benzo[1.3]dioxol-5-yl, 6-chloro-2H-chroman-3-yl, imidazolidin-2,4-dion-5-ylmethyl, cyclopropyl, cyclobutyl, cyclopentyl optionally attached via a - (CH2)- bridge or a -(CH2)2 bridge, cyclohexyl, 4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptyl and adamantyl.
  10. Compounds according to one or more of claims 1 to 9, characterized in that
    I.)
    R1 stands for a substituted six-membered or ten-membered aryl residue
    or for an optionally substituted five-membered to fourteen-membered heteroaryl residue;
    or for -(CH2)m-O-C(=O)-R5, where m is 1, 2, 3, 4, or 5;
    or for -(CH2)n-C(=O)-O-R6, where n is 1, 2, 3, 4, or 5;
    or for -(CH2)-R22;
    or for -(CH2)-(CH2)c-U-(CH2)d-R23, where c is 0 or 1 and d is 0 or 1 and in which U stands for O, S, NH, N(CH3), or N(C2H5);
    R2 stands for a hydrogen residue;
    or for -(CH2)-(CH2)e-Vf-(CH2)g-R24, where e is 0 or 1, f is 0 or 1, and g is 0 or 1 and in which V stands for O, S, NH, N(CH3), or N(C2H5);
    or for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an optionally substituted five-membered to fourteen-membered aryl residue or heteroaryl residue;
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-Ps-(CH2)t-(CH2)u-Qv-R11, where s is 0 or 1, t is 0 or 1, u is 0 or 1, and v is 0 or 1 and in which P and Q each independently stand for O, S, NH, N(CH3), or N(C2H5) and the sum of s and v is equal to 1;
    or for -(CR12R13)-(CH2)w-(CH2)x-C(=O)-O-R7, where w is 0 or 1 and x is 0 or 1;
    or for -(CR14R15)-(CH2)y-O-C(=O)-R8, where y is 0 or 1;
    or for -(CHR16)-(CH2)2-C(=O)-R9, where z is 0 or 1;
    or for -CH[(CH2)-Ta-(CH2)b-R17][NH-C(=O)-O-R18], where a is 0 or 1 and b is 0 or 1 and in which T stands for O, S, NH, N(CH3), or N(C2H5);
    or for -CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21 ;
    or for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an unsaturated or saturated, optionally substituted three-membered, four-membered, five-membered, six-membered, seven-membered, eight-membered or nine-membered cycloaliphatic residue, which can be fused with a saturated or unsaturated, optionally aromatic, optionally substituted monocyclic ring system and/or bridged by one or two linear or branched, optionally substituted C1-5-alkylene groups,
    or for an optionally substituted five-membered to fourteen-membered aryl residue or heteroaryl residue, which can be fused with a saturated or unsaturated, optionally substituted monocyclic ring system;
    or II.)
    R1 stands for a hydrogen residue
    or for an in each case linear or branched, in each case unsubstituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an unsubstituted phenyl residue or an unsubstituted benzyl residue;
    R2 stands for a hydrogen residue;
    or for -(CH2)-(CH2)e-Vf-(CH2)g-R24, where e is 0 or 1, f is 0 or 1, and g is 0 or 1 and in which V stands for O, S, NH, N(CH3), or N(C2H5);
    or for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an optionally substituted five-membered to fourteen-membered aryl or heteroaryl residue;
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-Ps-(CH2)t-(CH2)u-Qv-R11, where s is 0 or 1, t is 0 or 1, u is 0 or 1 and v is 0 or 1 and in which P and Q each stand independently for O, S, NH, N(CH3), or N(C2H5), and the sum of s and v is equal to 1;
    or for -(CR12R13)-(CH2)w-(CH2)x-C(=O)-O-R7, where w is 0 or 1 and x is 0 or 1;
    or for -(CR14R15)-(CH2)y-O-C(=O)-R8, where y is 0 or 1;
    or for -(CHR16)-(CH2)z-C(=O)-R9, where z is 0 or 1;
    or for -CH[(CH2)-Ta-(CH2)b-R17][NH-C(=O)-O-R18], where a is 0 or 1 and b is 0 or 1 and in which T stands for O, S, NH, N(CH3), or N(C2H5);
    or for -CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21;
    or for a linear or branched, substituted C1-10-alkyl residue;
    or for a linear or branched, optionally substituted C2-10-alkenyl residue;
    or for a linear or branched, optionally substituted C2-10-alkynyl residue;
    or for an unsaturated or saturated, optionally substituted three-membered, four-membered, five-membered, six-membered, seven-membered, eight-membered or nine-membered cycloaliphatic residue, which can be fused with a saturated or unsaturated, optionally aromatic, optionally substituted monocyclic ring system and/or bridged by one or two linear or branched, optionally substituted C1-5 alkylene groups;
    or for a phenyl residue, which is substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of -CN, -SF5, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-C1-5-alkyl, -C(=O)-OH, -C(=O)-O-C1-5-alkyl,-O-C(=O)-C1-5-alkyl, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-C1-5-alkyl, -(CH2)-O-C(=O)-phenyl, -NH-C1-5-alkyl, -N(C1-5-alkyl)2, -NH-C(=O)-O-C1-5-alkyl, -NH-C(=O)-C1-5-alkyl,-C(=O)-H, -C(=O)-C1-5-alkyl, -C(=O)-NH2, -C(=O)-NH-C1-5-alkyl, C(=O)-N-(C1-5-alkyl)2,-S(=O)2-NH2, -S(=O)2-NH-C1-5-alkyl, -S(=O)2-NH-phenyl, -(CH2)benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-C1-5-alkyl, -C1-5-alkyl, O-CF3, -S-CF3, phenyl and O-benzyl,
    or for a residue selected from the group consisting of 1,2,3,4,5-pentafluorophenyl, 1,2,3,4-tetrafluorophenyl, 4-methyl-3-nitrophenyl, 5-methyl-3-nitrophenyl, 6-methyl-3-nitrophenyl, and 2-methyl-3-nitrophenyl;
    or for an unsubstituted naphthyl residue;
    or for an optionally substituted six-membered or ten-membered aryl residue, which is fused with a saturated or unsaturated, optionally substituted monocyclic ring system;
    or for an optionally substituted five-membered to fourteen-membered heteroaryl residue, which can be fused with a saturated or unsaturated, optionally substituted monocyclic ring system;
    or III.)
    R1 stands for a hydrogen residue;
    or for an in each case linear or branched, in each case unsubstituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an optionally substituted five-membered to fourteen-membered aryl or heteroaryl residue;
    or for -(CH2)m-O-C(=O)-R5 where m is 1, 2, 3, 4, or 5;
    or for -(CH2)n-C(=O)-O-R6, where n is 1, 2, 3, 4, or 5;
    or for an unsubstituted benzyl residue;
    or for -(CH2)-R22;
    or for -(CH2)-(CH2)c-U-(CH2)d-R23, where c is 0 or 1 and d is 0 or 1 and in which U stands for O, S, NH, N(CH3), or N(C2H5);
    R2 stands for -(CH2)-(CH2)e-V-(CH2)g-R24 where e is 0 or 1 and g is 0 or 1 and in which V stands for S, NH, N(CH3), or N(C2H5);
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-Ps-(CH2)t-(CH2)uQv-R11 where s is 0 or 1, t is 0 or 1, u is 0 or 1 and v is 0 or 1 and in which P and Q each stand independently for O, S, NH, N(CH3), or N(C2H5) and the sum of s and v is equal to 1;
    or for -(CR12R13)-(CH2)w-(CH2)x-C(=O)-O-R7, where w is 0 or 1 and x is 0 or 1;
    or for -(CR14R15)-(CH2)y-O-C(=O)-R8, where y is 0 or 1;
    or for -(CHR16)-(CH2)z-C(=O)-R9, where z is 0 or 1;
    or for CH[(CH2)-Ta-(CH2)b-R17][NH-C(=O)-O-R18], where a is 0 or 1 and b is 0 or 1 and in which T stands for O, S, NH, N(CH3), or N(C2H5);
    or for CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21 ;
    or for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an unsaturated or saturated, optionally substituted three-membered, four-membered, five-membered, six-membered, seven-membered, eight-membered or nine-membered cycloaliphatic residue, which can be fused with a saturated or unsaturated, optionally aromatic, optionally substituted monocyclic ring system and/or bridged by one or two linear or branched, optionally substituted C1-5-alkylene groups,
    or for an optionally substituted five-membered to fourteen-membered aryl residue or heteroaryl residue, which can be fused with a saturated or unsaturated, optionally substituted monocyclic ring system;
    and in each case, if present, in the aforementioned groups I.), II.) and III.) the residues
    R5, R6, and R9, and R18 each independently
    stand for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    R7 stands for a hydrogen residue
    or for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an optionally substituted five-membered to fourteen-membered aryl residue or an optionally substituted five-membered to fourteen-membered heteroaryl residue;
    R8, R16, and R24 each independently
    stand for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an optionally substituted five to fourteen-membered aryl residue or an optionally substituted five to fourteen-membered heteroaryl residue;
    R10, R12, and R13 each independently
    stand for a hydrogen residue;
    or for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    R11 stands for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an unsaturated or saturated, optionally substituted three-membered, four-membered, five-membered, six-membered, seven-membered, eight-membered, or nine-membered cycloaliphatic residue;
    or for an optionally substituted six-membered or ten-membered aryl residue;
    R14, R15, and R19 each independently
    stand for a hydrogen residue;
    or for an in each case linear or branched, in each case optionally substituted C1-10-alkyl residue, C2-10-alkenyl residue or C2-10-alkynyl residue;
    or for an optionally substituted six-membered or ten-membered aryl residue;
    R17 and R21 each independently
    stand for an optionally substituted six-membered or ten-membered aryl residue;
    R20 stands for an unsaturated or saturated, optionally substituted three-membered, four-membered, five-membered, six-membered, seven-membered, eight-membered or nine-membered cycloaliphatic residue
    or for an optionally substituted six-membered or ten-membered aryl residue;
    R22 stands for a substituted six-membered aryl residue
    or for an optionally substituted ten-membered aryl residue
    or for an optionally substituted heteroaryl residue;
    and
    R23 stands for an optionally substituted five to fourteen-membered aryl residue or an optionally substituted five to fourteen-membered heteroaryl residue;
    wherein
    the aforementioned C1-10-alkyl residues can be unsubstituted or can in each case be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, and -N(C1-5-alkyl)-(C1-5-alkyl);
    the aforementioned C2-10-alkenyl residues can be unsubstituted or can in each case be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, - NO2, -OH, -SH, -NH2, and -N(C1-5-alkyl)-(C1-5-alkyl);
    the aforementioned C2-10-alkynyl residues can be unsubstituted or can in each case be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, - NO2, -OH, -SH, -NH2, and -N(C1-5-alkyl)-(C1-5-alkyl);
    the aforementioned C1-5-alkylene groups can be unsubstituted or can in each case be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -SH, - NH2, -CN, NO2, and phenyl,
    the aforementioned cycloaliphatic residues can be unsubstituted or in each case substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo (=O), thioxo (=S), F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-C1-5-alkyl, -NH2, -NO2, -O-CF3, -S-CF3, -SH, -S-C1-5 alkyl, -C1-5-alkyl,-C(=O)-H, -C(=O)-C1-5-alkyl, -C(=O)-OH, -C(=O)-O-C1-5-alkyl, -(CH2)-C(=O)-OH, -(CH2)-C(=O)-O-C1-5-alkyl, -NH-C1-5-alkyl, -N(C1-5-alkyl)2, -(CH2)benzo[b]furanyl, -O-phenyl, -O-benzyl, phenyl, benzyl, naphthyl, and -(CH2)-naphthyl, wherein in each case the cyclic moiety of the residues -O-phenyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, benzyl, naphthyl, and -(CH2)-naphthyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, - SF5, -CN, -NO2, -O-C1-5-alkyl, -C1-5-alkyl, -O-CF3, -S-CF3, phenyl, and -O-benzyl,
    and the aforementioned cycloaliphatic residues can in each case comprise 1, 2, 3, 4, or 5 heteroatom(s) independently selected from the group consisting of oxygen, nitrogen, and sulfur;
    the ring of the aforementioned monocyclic ring systems can be optionally unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo (=O), thioxo (=S), F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-C1-5-alkyl, -O-C2-5-alkenyl, -NH2, -NO2, -O-CF3, -O-CHF2, - O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-C1-5-alkyl, -C1-5-alkyl, -C(=O)-OH, -C(=O)-O-C1-5-alkyl, -0-C(=O)-C1-5-alkyl, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-C1-5-alkyl, -(CH2)-O-C(=O)-phenyl, -NH-C1-5-alkyl, -N(C1-5-alkyl)2, -NH-C(=O)-O-C1-5-alkyl, -NH-C(=O)-C1-5-alkyl, -C(=O)-H, -C(=O)-C1-5-alkyl, -C(=O)-NH2, -C(=O)-NH-C1-5-alkyl, C(=O)-N-(C1-5-alkyl)2, -S(=O)2-NH2, -S(=O)2-NH-C1-5-alkyl, -S(=O)2-NH-phenyl, -(CH2)benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, - S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-C1-5-alkyl, -C1-5-alkyl, -O-CF3, -S-CF3, phenyl und -O-benzyl,
    and the ring of the aforementioned monocyclic ring systems is in each case five-membered, six-membered, or seven-membered and can comprise 1, 2, 3, 4, or 5 heteroatom(s) as ring member(s), which are independently selected from the group consisting of oxygen, nitrogen, and sulfur;
    and, unless otherwise stated, the aforementioned aryl residues or heteroaryl residues can be unsubstituted or in each case substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-C1-5-alkyl, -O-C2-5-alkenyl, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-C1-5-alkyl, -C1-5-alkyl, -C(=O)-OH, -C(=O)-O-C1-5-alkyl, -O-C(=O)-C1-5-alkyl, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-C1-5-alkyl, -(CH2)-O-C(=O)-phenyl, -NH-C1-5-alkyl, -N(C1-5-alkyl)2, -NH-C(=O)-O-C1-5-alkyl, -NH-C(=O)-C1-5-alkyl, -C(=O)-H, -C(=O)-C1-5-alkyl, -C(=O)-NH2, -C(=O)-NH-C1-5-alkyl, C(=O)-N-(C1-5-alkyl)2, -S(=O)2-NH2, -S(=O)2-NH-C1-5-alkyl, - S(=O)2-NH-phenyl, -(CH2)benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)benzo[b]furanyl und benzyl can be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-C1-5-alkyl, -C1-5-alkyl, -O-CF3, -S-CF3, phenyl und -O-benzyl,
    and
    the aforementioned heteroaryl residues can in each case comprise 1, 2, 3, 4, or 5 heteroatom(s) independently selected from the group consisting of oxygen, nitrogen, and sulfur, as ring member(s);
    in each case optionally in the form of one of the pure stereoisomers thereof, particularly enantiomers or diastereoisomers thereof, the racemates thereof or in the form of a mixture of stereoisomers, particularly the enantiomers and/or diastereoisomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.
  11. Compounds according to claim 10, characterized in that
    I.)
    R1 stands for a phenyl or naphthyl residue, which is in each case substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN,-CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3,-O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F,-SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3,-C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -O-C(=O)-phenyl,-(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, N(C2H5)2, -N(H)(CH3), -N(H)C2H5), -NH-C(=O)-)-CH3, NH-C(=O)-O-C2H5, NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3,-C(=O)-NH-C2H5, S(=O)2-NH2, S(=O)2-NH-CH3, -S(=O)2NH-C2H5, S(=O)2-NH=phenyl,-(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, wherein in each case the cyclic moiety of the residues O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN,-NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl, and -O-benzyl,
    or for a heteroaryl residue selected from the group consisting of thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, and isoquinolinyl, wherein the heteroaryl residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5,-C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-O-C2H5, -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3, -C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, and in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN,-NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl, and -O-benzyl,
    or for -(CH2)m-O-C(=O)-R5, where m is 1, 2, 3, 4, or 5;
    or for -(CH2)n-C(=O)-O-R6, where n is 1, 2, 3, 4, or 5;
    or for -(CH2)-R22;
    or for -(CH2)-O-R23, -(CH2)-S-R23, -(CH2)-N(CH3)-R23, -(CH2)-(CH2)-O-R23, -(CH2)-(CH2)-S-R23, -(CH2)-(CH2)-NH-R23, -(CH2)-(CH2)-N(CH3)-R23, -(CH2)-(CH2)-O-(CH2)-R23, -(CH2)-(CH2)-S-(CH2)-R23, or -(CH2)-(CH2)-N(CH3)-R23;
    R2 stands for a hydrogen residue;
    or for -(CH2)-R24, -(CH2)-O-R24, -(CH2)-S-R24, -(CH2)-N(CH3)-R24, -(CH2)-(CH2)-R24, -(CH2)-(CH2)-O-R24, -(CH2)-(CH2)-S-R24, -(CH2)-(CH2)-NH-R24, -(CH2)-(CH2)-N(CH3)-R24, (CH2)-(CH2)-(CH2)-R24, -(CH2)-(CH2)-O-(CH2)-R24, -(CH2)-(CH2)-S-(CH2)-R24, or-(CH2)-(CH2)-N(CH3)-R24;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, sec-pentyl, -(CH2)-(CH2)-(C(CH3)3), n-hexyl, n-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and 3-butynyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and -N-(CH3)-(C2H5);
    or for a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, and isoquinolinyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5,-C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2,-N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-O-C2H5, -NH-C(=O)-CH3,-NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3,-C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl,-(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH,-CF3, -SF5, -CN, -NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl and-O-benzyl,
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-O-R11, -(CHR10)-S-R11, -(CHR10)-NH-R11, -(CHR10)-O-(CH2)-R11, -(CHR10)-S-(CH2)-R11, -(CHR10)-NH-(CH2)-R11, -(CHR10)-N(CH3)-(CH2)-R11, -(CHR10)-(CH2)-(CH2)-O-R11, -(CHR10)-(CH2)-(CH2)-S-R11, -(CHR10)-(CH2)-(CH2)-NH-R11-(CHR10)-(CH2)-(CH2)-N(C2H5)-R11, -(CHR10)-O-(CH2)-(CH2)-O-R11, -(CHR10)-S-(CH2)-(CH2)-S-R11,-(CHR10)-O-(CH2)-(CH2)-S-R11 or -(CHR10)-S-(CH2)-(CH2)-O-R11,
    or for -(CR12R13)-C(=O)-O-R7, -(CR12R13)-(CH2)-C(=O)-O-R7, or -(CR12R13)-(CH2)-(CH2)-C(=O)-O-R7;
    or for -(CR14R15)-O-C(=O)-R8 or -(CR14R5)-(CH2) -O-C(=O)-R8;
    or for -(CHR16)-C(=O)-R9 or -(CHR16)-(CH2)-C(=O)-R9;
    or for CH[(CH2)-O-(CH2)-R17][NH-C(=O)-O-R18] or -CH[(CH2)-S-(CH2)-R17][NH-C(=O)-O-R18;
    or for CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, n-octyl, -(CH2)-(CH)-(C2Hs)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and N-(CH3)-(C2H5);
    or for a (hetero)cycloaliphatic residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl, tetrahydropyranyl, azepanyl, diazepanyl, dithiolanyl, adamantyl, and 7,7-dimethyl-2-oxa-bicyclo[2.2.1]heptyl, wherein the (hetero)cycloaliphatic residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo (=O), thioxo (=S), F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-C(CH3)3, -NH2,-NO2, -O-CF3, -S-CF3, -SH, S-CH3, -S-C2H5, -S-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -(CH2)-C(=O)-OH,-(CH2)-C(=O)-O-CH3, -(CH2)-C(=O)-O-C2H5, -N(CH3)2, -N(C2H5)2, -N(H)(CH3),-N(H)(C2H5), -(CH2)-benzo[b]furanyl, -O-phenyl, -O-benzyl, phenyl, benzyl, naphthyl, and -(CH2)-naphthyl, wherein in each case the cyclic moiety of the residues -O-phenyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, benzyl, naphthyl, and -(CH2)-naphthyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-CH3, -O-C2H5, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl and-O-benzyl,
    or for a residue selected from the group consisting of phenyl, naphthyl, (1,3)-benzodioxolyl, (1,4)-benzodioxanyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, isoquinolinyl, phenazinyl, phenothiazinyl, oxadiazolyl, benzo[1,2,5]oxadiazolyl, and chromanyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -O-C(=O)-CH3,-O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3,-NH-C(=O)-O-C2H5, -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3, -C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3,-S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents selected independently from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2. -O-CH3, -O-C2H5, -O-CH(CH3)2,-O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl,-O-CF3, -S-CF3, phenyl, and -O-benzyl,
    or II.)
    R1 stands for a hydrogen residue
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, sec-pentyl, -(CH2)-(CH2)-(C(CH3)3), n-hexyl, n-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and 3-butynyl;
    or for an unsubstituted phenyl residue or benzyl residue;
    R2 stands for a hydrogen residue;
    or for -(CH2)-R24, -(CH2)-O-R24, -(CH2)-S-R24, -(CH2)-N(CH3)-R24, -(CH2)-(CH2)-R24, -(CH2)-(CH2)-O-R24, -(CH2)-(CH2)-S-R24, -(CH2)-(CH2)-NH-R24, -(CH2)-(CH2)-N(CH3)-R24,-(CH2)-(CH2)-(CH2)-R24, -(CH2)-(CH2)-O-(CH2)-R24, -(CH2)-(CH2)-S-(CH2)-R24 or -(CH2)-(CH2)-N(CH3)-R24;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, sec-pentyl, -(CH2)-(CH2)-(C(CH3)3), n-hexyl, n-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and 3-butynyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2 and -N-(CH3)-(C2H5);
    or for a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, and isoquinolinyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5,-C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -0-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-O-C2H5, -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3 -C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN,-NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl and -O-benzyl,
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-O-R11, -(CHR10)-S-R11, -(CHR10)-NH-R11, -(CHR10)-O-(CH2)-R11, -(CHR10)-S-(CH2)-R11, -(CHR10)-NH-(CH2)-R11, -(CHR10)-N(CH3)-(CH2)-R11, -(CHR10)-(CH2)-(CH2)-O-R11, -(CHR10)-(CH2)-(CH2)-S-R11, -(CHR10)-(CH2)-(CH2)-NH-R11-(CHR10)-(CH2)-(CH2)-N(C2H5)-R11, -(CHR10)-O-(CH2)-(CH2)-O-R11, -(CHR10)-S-(CH2)-(CH2)-S-R11,-(CHR10)-O-(CH2)-(CH2)-S-R11 or -(CHR10-S-(CH2-(CH2)-O-R11,
    or for -(CR12R13)-C(=O)-O-R7, -(CR12R13)-(CH2)-C(=O)-O-R7, or -(CR12R13)-(CH2)-(CH2)-C(=O)-O-R7;
    or for -(CR14R15)-O-C(=O)-R8 or -(CR14R15)-(CH2), and -O-C(=O)-R8;
    or for -(CHR16)-C(=O)-R9 or -(CHR16)-(CH2)-C(=O)-R9;
    or for -CH[(CH2)-O-(CH2)-R11][NH-C(=O)-O-R18] or -CH[(CH2)-S-(CH2)-R17][NH-C(=O)-O-R18;
    or for -CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21;
    or for an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, n-octyl, and -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), wherein the alkyl residue is in each case substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and-N-(CH3)-(C2H5);
    or for a residue selected from the group consisting of vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and 3-butynyl, wherein residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN,-NO2, -OH, -SH, -NH2, -N-(CH3)2, -N(C2H5)2, and -N-(CH3)-(C2H5);
    or for a (hetero)cycloaliphatic residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl, tetrahydropyranyl, azepanyl, diazepanyl, dithiolanyl, adamantyl, and 7,7-dimethyl-2-oxa-bicyclo[2.2.1]heptyl, wherein the (hetero)cycloaliphatic residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo (=O), thioxo (=S), F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-C(CH3)3, -NH2,-NO2, -O-CF3, -S-CF3, -SH, S-CH3, -S-C2H5, -S-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -(CH2)-C(=O)-OH,-(CH2)-C(=O)-O-CH3, -(CH2)-C(=O)-O-C2H5, -N(CH3)2, -N(C2H5)2, -N(H)(CH3),-N(H)(C2H5), -(CH2)-benzo[b]furanyl, -O-phenyl, -O-benzyl, phenyl, benzyl, naphthyl, and -(CH2)-naphthyl, wherein in each case the cyclic moiety of the residues -O-phenyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, benzyl, naphthyl, and -(CH2)-naphthyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-CH3, -O-C2H5, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl, and -O-benzyl,
    or for a phenyl residue, wherein the phenyl residue can be substituted in each case with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of -CN,-SF5, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2,-N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-O-C2H5, -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2,-C(=O)-NH-CH3, -C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5,-S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl and benzyl can be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl and -O-benzyl,
    or for a residue selected from the group consisting of 1,2,3,4,5-pentafluorophenyl, 1,2,3,4-tetrafluorophenyl, 4-methyl-3-nitrophenyl, 5-methyl-3-nitrophenyl, 6-methyl-3-nitrophenyl, and 2-methyl-3-nitrophenyl;
    or for an unsubstituted naphthyl residue;
    or for a residue selected from the group consisting of (1,3)-benzodioxolyl and (1,4)-benzodioxanyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl;
    or for a heteroaryl residue selected from the group consisting of thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, isoquinolinyl, phenazinyl, phenothiazinyl, oxadiazolyl, benzo[1,2,5]oxadiazolyl, and chromanyl, wherein the heteroaryl residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2,-N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-O-C2H5, -NH-C(=O)-CH3,-NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3,-C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl,-(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH,-CF3, -SF5, -CN, -NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl, and-O-benzyl,
    or III.)
    R1 stands for a hydrogen residue;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, sec-pentyl, -(CH2)-(CH2)-(C(CH3)3), n-hexyl, n-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and 3-butynyl;
    or for a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, and isoquinolinyl, wherein the heteroaryl residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5,-C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-0-C2H5, -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3, -C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)-Benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN,-NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl, and -O-benzyl,
    or for -(CH2)m-O-C(=O)-R5, where m is 1, 2, 3, 4, or 5;
    or for -(CH2)n-C(=O)-O-R6, where n is 1, 2, 3, 4, or 5;
    or for an unsubstituted benzyl residue;
    or for -(CH2)-R22;
    or for -(CH2)-O-R23, -(CH2)-S-R23, -(CH2)-N(CH3)-R23, -(CH2)-(CH2)-O-R23, -(CH2)-(CH2)-S-R23, -(CH2)-(CH2)-NH-R23, -(CH2)-(CH2)-N(CH3)-R23, -(CH2)-(CH2)-O-(CH2)-R23, -(CH2)-(CH2)-S-(CH2)-R23, or -(CH2)-(CH2)-N(CH3)-R23;
    R2 stands for -(CH2)-S-R24, -(CH2)-N(CH3)-R24, -(CH2)-(CH2)-S-R24, -(CH2)-(CH2)-NH-R24, -(CH2)-(CH2)-N(CH3)-R24, -(CH2)-(CH2)-S-(CH2)-R24, or -(CH2)-(CH2)-N(CH3)-R24;
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-O-R11, -(CHR10)-S-R11, -(CHR10)-O-(CH2)-R11, -(CHR10)-S-(CH2)-R11,-(CHR10)-(CH2)-(CH2)-O-R11, -(CHR10)-(CH2)-(CH2)-S-R11, or -(CHR10)-O-(CH2)-(CH2)-O-R11,
    or for -(CR12R13)-C(=O)-O-R7 or -(CR12R13)-(CH2)-C(=O)-O-R7;
    or for -(CR14R15)-O-C(=O)-R8 or -(CR14R15)-(CH2), and -O-C(=O)-R8;
    or for -(CHR16)-C(=O)-R9 ;
    or for CH[(CH2)-O-(CH2)-R17][NH-C(=O)-O-R18];
    or for CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and N-(CH3)-(C2H5);
    or for a (hetero)cycloaliphatic residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, thiomorpholinyl, tetrahydropyranyl, azepanyl, diazepanyl, dithiolanyl, adamantyl, and 7,7-dimethyl-2-oxa-bicyclo[2.2.1]heptyl, wherein the (hetero)cycloaliphatic residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo (=O), thioxo (=S), F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-C(CH3)3, -NH2,-NO2, -O-CF3, -S-CF3, -SH, S-CH3, -S-C2H5, -S-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -(CH2)-C(=O)-OH,-(CH2)-C(=O)-O-CH3, -(CH2)-C(=O)-O-C2H5, -N(CH3)2, -N(C2H5)2, -N(H)(CH3),-N(H)(C2H5), -(CH2)-benzo[b]furanyl, -O-phenyl, -O-benzyl, phenyl, benzyl, naphthyl, and -(CH2)-naphthyl, wherein in each case the cyclic moiety of the residues -O-phenyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, benzyl, naphthyl, and -(CH2)-naphthyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-CH3, -O-C2H5, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl, and-O-benzyl,
    or for a residue selected from the group consisting of phenyl, naphthyl, (1,3)-benzodioxolyl, (1,4)-benzodioxanyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, isoquinolinyl, phenazinyl, phenothiazinyl, oxadiazolyl, benzo[1,2,5]oxadiazolyl und chromanyl, wherein the residue can in each case be substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -O-C(=O)-CH3,-O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3,-NH-C(=O)-O-C2H5, -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3, -C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3,-S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl,-S-benzyl, -O-benzyl, phenyl und benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN, -NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2,-O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl,-O-CF3, -S-CF3, phenyl, and -O-benzyl,
    and in each case, if present, in the aforementioned groups I.) II.) and III.) the residues
    R5, R6, R9 and R18 each independently
    stand for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CHZ)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and -N-(CH3)-(C2H5);
    R7 stands for a hydrogen residue;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and N-(CH3)-(C2H5);
    or for a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyrazinyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, isoquinolinyl, phenazinyl, phenothiazinyl, oxadiazolyl, benzo[1,2,5]oxadiazolyl, and chromanyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO 2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5,-C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-O-C2H5, -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3, -C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl, -(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH, -CF3, -SF5, -CN,-NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl, and -O-benzyl,
    R8, R16, and R24 each independently
    stand for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and N-(CH3)-(C2H5);
    or for a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrazinyl, pyrimidinyl, indazolyl, quinazolinyl, quinolinyl, isoquinolinyl, phenazinyl, phenothiazinyl, oxadiazolyl, benzo[1,2,5]oxadiazolyl, and chromanyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -O-C(=O)-phenyl, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2,-N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-O-C2H5, -NH-C(=O)-CH3,-NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2, -C(=O)-NH-CH3,-C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5, -S(=O)2-NH-phenyl, -(CH2)-benzo[b]furanyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, and benzyl, wherein in each case the cyclic moiety of the residues -O-C(=O)-phenyl,-(CH2)-O-C(=O)-phenyl, -S(=O)2-NH-phenyl, -O-phenyl, -S-phenyl, -S-benzyl, -O-benzyl, phenyl, -(CH2)-benzo[b]furanyl, and benzyl can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -OH,-CF3, -SF5, -CN, -NO2, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-CF3, -S-CF3, phenyl, and-O-benzyl,
    R10, R12, and R13 each independently
    stand for a hydrogen residue
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and -N-(CH3)-(C2H5);
    R11 stands for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-Heptyl, 3-heptyl, 4-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl und 3-butenyl, wherein the residue can be substituted in each case by 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of F, Cl, Br, I,-CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2 und -N(CH3)-(C2H5);
    or for a (hetero)cycloaliphatic residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, imidazolidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, and diazepanyl, wherein the (hetero)cycloaliphatic residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo (=O), thioxo (=S), F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-C(CH3)3, -NH2, -NO2, -O-CF3, -S-CF3, -SH, S-CH3, -S-C2H5, -S-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-H,-C(=O)-CH3, -C(=O)-C2H5, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, and -C(=O)-O-C(CH3)3,
    or for a phenyl or naphthyl residue, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, and phenyl;
    R14, R15, and R19 each independently
    stand for a hydrogen residue;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, n-octyl, -(CH2)-(CH)-(C2H5)-(CH2)-(CH2)-(CH2)-(CH3), vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, and 3-butenyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -NO2, -OH, -SH, -NH2, -N(CH3)2, -N(C2H5)2, and N-(CH3)-(C2H5);
    or for a phenyl residue or naphthyl residue, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert.-butyl;
    R20 stands for a (hetero)cycloaliphatic residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, imidazolidinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, azepanyl, and diazepanyl, wherein the (hetero)cycloaliphatic residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo (=O), thioxo (=S), F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-C(CH3)3, -NH2, -NO2, -O-CF3, -S-CF3, -SH, S-CH3, -S-C2H5, -S-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-H,-C(=O)-CH3, -C(=O)-C2H5, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, and -C(=O)-O-C(CH3)3;
    or for a phenyl or naphthyl residue, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, and phenyl;
    R17 and R21 each independently
    stand for a phenyl or naphthyl residue, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert.-butyl;
    R22 stands for a phenyl residue, wherein the phenyl residue is in each case substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I,-CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, -C(=O)-O-C(CH3)3, -O-C(=O)-CH3, -O-C(=O)-C2H5, -N(CH3)2,-N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-O-CH3, -NH-C(=O)-O-C2H5, -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -C(=O)-H, -C(=O)-CH3, -C(=O)-C2H5, -C(=O)-NH2,-C(=O)-NH-CH3, -C(=O)-NH-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3 and -S(=O)2-NH-C2H5,
    or for a naphthyl residue, wherein the naphthyl residue can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN,-CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3,-O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F,-SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert.-butyl;
    or for a heteroaryl residue selected from the group consisting of thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrazinyl, pyrimidinyl, indazolyl, quinazolinyl, and quinolinyl, wherein the heteroaryl residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3,-O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2Hs, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, and -C(=O)-O-C(CH3)3,
    and
    R23 stands for a residue selected from the group consisting of phenyl, naphthyl, thiophenyl, furanyl, pyrrolyl, pyrazolyl, pyranyl, triazolyl, pyridinyl, imidazolyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyridazinyl, pyrazinyl, pyrimidinyl, indazolyl, quinazolinyl, and quinolinyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -SF5, -OH, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, -O-CH2-CH2-CH2-CH3, -O-CH2-CH=CH2, -NH2, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -SH, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, -S-CH2-CH2-CH2-CH3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, -C(=O)-O-CH3, -C(=O)-O-C2H5, and-C(=O)-O-C(CH3)3.
  12. Compounds according to claim 10 or claim 11, characterized in that
    I.)
    R1 stands for -(CH2)mO-C(=O)-R5 where m is 1, 2, 3, or 4;
    or for -(CH2)n-C(=O)-O-R6, where n is 1, 2 or 3;
    or for -(CH2)-R22;
    or for -(CH2)-(CH2)-O-R23, -(CH2)-(CH2)-S-R23, -(CH2)-(CH2)-NH-R23, or -(CH2)-(CH2)-N(CH3)-R23;
    R2 stands for a hydrogen residue;
    or for -(CH2)-R24, -(CH2)-(CH2)-R24, -(CH2)-(CH2)-O-R24, -(CH2)-(CH2)-S-R24, or -(CH2)-(CH2)-(CH2)-R24;
    or for an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, and sec-pentyl;
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-O-R11, -(CHR10)-S-R11, -(CHR10)-O-(CH2)-R11, -(CHR10)-S-(CH2)-R11,-(CHR10)-(CH2)-(CH2)-O-R11, -(CHR10)-(CH2)-(CH2)-S-R11, or -(CHR10)-O-(CH2)-(CH2)-O-R11,
    or for -(CR12R13)-C(=O)-O-R7 or -(CR12R13)-(CH2)-C(=O)-O-R7;
    or for -(CR14R15)-O-C(=O)-R8 or -(CR14R15)-(CH2)-O-C(=O)-R8;
    or for -(CHR16)-C(=O)-R9;
    or for -CH[(CH2)-O-(CH2)-R17][NH-C(=O)-O-R18];
    or for -CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, -(CH2)-N(CH3)2,-(CH2)-(CH2)-N(CH3)2, 1-butenyl, 2-butenyl, and 3-butenyl;
    or for a (hetero)cycloaliphatic residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, adamantyl, and 7,7-dimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptyl, and the cycloaliphatic residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents methyl, ethyl, and n-propyl;
    or for a residue selected from the group consisting of phenyl, naphthyl, (1,3)-benzodioxolyl, (1,4)-benzodioxanyl, thiophenyl, furanyl, pyrazolyl, triazolyl, pyridinyl, imidazolyl, indolyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyrimidinyl, oxadiazolyl, benzo[1,2,5]oxadiazolyl, and chromanyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -O-CH3, -O-C2H5, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -(CH2)-O-C(=O)-CH3,-(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -NH-C(=O)-CH3,-NH-C(=O)-C2H5, -S(=O)2-NH2, -O-phenyl, and phenyl, wherein the cyclic moiety of the residues -O-phenyl and phenyl can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, methyl, ethyl, n-propyl, and isopropyl.
    or II.)
    R1 stands for a hydrogen residue
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, 1-propynyl, and 2-propynyl;
    or for an unsubstituted benzyl residue;
    R2 stands for a hydrogen residue;
    or for -(CH2)-R24, -(CH2)-(CH2)-R24, -(CH2)-(CH2)-O-R24, -(CH2)-(CH2)-S-R24, or -(CH2)-(CH2)-(CH2)-R24;
    or for an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, and sec-pentyl;
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-O-R11, -(CHR10)-S-R11, -(CHR10)-O-(CH2)-R11, -(CHR10)-S-(CH2)-R11,-(CHR10)-(CH2)-(CH2)-O-R11, -(CHR10)-(CH2)-(CH2)-S-R11, or -(CHR10)-O-(CH2)-(CH2)-O-R11,
    or for -(CR12R13)-C(=O)-O-R7 or -(CR12R13)-(CH2)-C(=O)-O-R7;
    or for -(CR10R15)-O-C(=O)-R8 or -(CR14R15)-(CH2)-O-C(=O)-R8;
    or for -(CHR16)-C(=O)-R9;
    or for -CH[(CH2)-O-(CH2)-R17][NH-C(=O)-O-R18];
    or for -CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21;
    or for a residue selected from the group consisting of -(CH2)-N(CH3)2, -(CH2)-(CH2)-N(CH3)2, 1-butenyl, 2-butenyl, and 3-butenyl;
    or for a (hetero)cycloaliphatic residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, adamantyl, and 7,7-dimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptyl, wherein the cycloaliphatic residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents methyl, ethyl, and n-propyl;
    or for a phenyl residue, wherein the phenyl residue is in each case substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of -CN, -NO2,-O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -(CH2)-O-C(=O)-CH3, -(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -N(H)(CH3), -N(H)(C2H5), -NH-C(=O)-CH3, -NH-C(=O)-C2H5, -S(=O)2-NH2, -S(=O)2-NH-CH3, -S(=O)2-NH-C2H5, and phenyl, wherein the cyclic moiety of the residues -(CH2)-O-C(=O)-phenyl and phenyl can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, and tert.-butyl,
    or for a residue selected from the group consisting of 1,2,3,4,5-pentafluorophenyl, 1,2,3,4-tetrafluorophenyl, 4-methyl-3-nitrophenyl, 5-methyl-3-nitrophenyl, 6-methyl-3-nitrophenyl, and 2-methyl-3-nitrophenyl;
    or for an unsubstituted naphthyl residue;
    or for an unsubstituted residue selected from the group consisting of (1,3)-benzodioxolyl and (1,4)-benzodioxanyl,
    or for a heteroaryl residue selected from the group consisting of thiophenyl, furanyl, pyrazolyl, triazolyl, pyridinyl, imidazolyl, indolyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyrimidinyl, oxadiazolyl, benzo[1,2,5]oxadiazolyl, and chromanyl, wherein the heteroaryl residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -O-CH3,-O-C2H5, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -O-phenyl, and phenyl, wherein the cyclic moiety of the residues-O-phenyl and phenyl can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, methyl, ethyl, n-propyl, and isopropyl;
    or III.)
    R1 stands for a hydrogen residue
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-2-butenyl, 1-propynyl, and 2-propynyl;
    or for -(CH2)m-O-C(=O)-R5, where m is 1, 2, 3, or 4;
    or for -(CH2)n-C(=O)-O-R6, where n is 1, 2 or 3;
    or for -(CH2)n-C(=O)-O-R6, where n is 1, 2 or 3;
    or for an unsubstituted benzyl residue;
    or for -(CH2)-R22;
    or for -(CH2)-(CH2)-O-R23, -(CH2)-(CH2)-S-R23, -(CH2)-(CH2)-NH-R23, or -(CH2)-(CH2)-N(CH3)-R23;
    R2 stands for -(CH2)-(CH2)-S-R24;
    R3 stands for a -C(=O)-R4 group;
    and
    R4 stands for -(CHR10)-O-R11, -(CHR10)-S-R11, -(CHR10)-O-(CH2)-R11, -(CHR10)-S-(CH2)-R11,-(CHR10)-(CH2)-(CH2)-O-R11, -(CHR10)-(CH2)-(CH2)-S-R11, or -(CHR10)-O-(CH2)-(CH2)-O-R11,
    or for -(CR12R13)-C(=O)-O-R7 or -(CR12R13)-(CH2)-C(=O)-O-R7;
    or for -(CR14R15)-O-C(=O)-R8 or -(CR14R15)-(CH2) -O-C(=O)-R8;
    or for -(CHR16)-C(=O)-R9;
    or for CH[(CH2)-O-(CH2)-R17][NH-C(=O)-O-R18];
    or for CHR19R20 or -(CH2)-CHR19R20;
    or for -(CH=CH)-R21;
    or for a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, n-pentyl, 2-pentyl, 3-pentyl, -(CH2)-(C(CH3)3), n-hexyl, 3-hexyl, -(CH2)-(CH2)-(C(CH3)3), n-heptyl, 3-heptyl, 4-heptyl, -(CH2)-N(CH3)2,-(CH2)-(CH2)-N(CH3)2, 1-butenyl, 2-butenyl, and 3-butenyl;
    or for a (hetero)cycloaliphatic residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, adamantyl, and 7,7-dimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptyl, wherein the cycloaliphatic residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents methyl, ethyl, and n-propyl;
    or for a residue selected from the group consisting of phenyl, naphthyl, (1,3)-benzodioxolyl, (1,4)-benzodioxanyl, thiophenyl, furanyl, pyrazolyl, triazolyl, pyridinyl, imidazolyl, indolyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyrimidinyl, oxadiazolyl, benzo[1,2,5]oxadiazolyl, and chromanyl, wherein the residue can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, I, -CN, -CF3, -O-CH3, -O-C2H5, -NO2, -O-CF3, -O-CHF2, -O-CH2F, -S-CF3, -S-CHF2, -S-CH2F, -S-CH3, -S-C2H5, -S-CH(CH3)2, -S-C(CH3)3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -(CH2)-O-C(=O)-CH3,-(CH2)-O-C(=O)-C2H5, -(CH2)-O-C(=O)-phenyl, -N(CH3)2, -N(C2H5)2, -NH-C(=O)-CH3,-NH-C(=O)-C2H5, -S(=O)2-NH2, -O-phenyl, and phenyl, wherein the cyclic moiety of the residues -O-phenyl and phenyl can in each case be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, methyl, ethyl, n-propyl, and isopropyl;
    and in each case, if present, in the aforementioned groups I.) II.) and III.) the residue(s)
    R5 stands for a methyl or ethyl residue;
    R6 stands for a methyl or ethyl residue;
    R7 stands for a hydrogen residue
    or for a methyl or ethyl residue;
    R8 stands for a methyl or ethyl residue
    or for an unsubstituted phenyl residue;
    R9 stands for a methyl or ethyl residue;
    R10 stands for a hydrogen residue
    or for a methyl or ethyl residue;
    R11 stands for a methyl or ethyl residue;
    or for a phenyl residue, which can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -O-CH3, -O-C2H5, -O-CH(CH3)2, -O-C(CH3)3, and phenyl;
    R12 stands for a hydrogen residue or for a methyl residue;
    R13 stands for a hydrogen residue or for a methyl residue;
    R14 stands for a hydrogen residue
    or for a methyl or ethyl residue
    or for an unsubstituted phenyl residue;
    R15 stands for a hydrogen residue or for a methyl residue.
    R16 stands for a methyl or ethyl residue
    or for an unsubstituted phenyl residue;
    R17 stands for an unsubstituted phenyl residue;
    R18 stands for an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, and tert.-butyl;
    R19 stands for a hydrogen residue
    or for a methyl or ethyl residue
    or for an unsubstituted phenyl residue;
    R20 stands for a residue selected from the group consisting of cyclopentyl, cyclohexyl, and hydantoin;
    or for a phenyl residue, which can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -O-CH3, -O-C2 H5, -O-CH(CH3)2, -O-C(CH3)3, and phenyl;
    R21 stands for a phenyl residue, which can be substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, and -CF3;
    R22 stands for a phenyl residue, wherein the phenyl residue is in each case substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of F, Cl, Br, -CN, -CF3, -NO2, -O-CF3, -S-CF3, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert.-butyl, -C(=O)-OH, and -C(=O)-O-CH3 -C(=O)-O-C2H5;
    or for an unsubstituted naphthyl residue;
    R23 stands for an unsubstituted phenyl residue
    and
    R24 stands for a methyl or ethyl residue
    or for an unsubstituted phenyl residue.
  13. Substituted 1,4,8-triazaspiro[4.5]decan-2-one compounds of the general formula I according to one or more of the previous claims 1 to 12 and selected from the group consisting of
    (1) 3-(S)-Benzyl-8-(2-ethylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (2) 8-(2,4-Dimethoxybenzoyl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (3) 3-(S,R)-Benzyl-8-(2-ethylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (4) 8-Acetyl-3-(S)-benzyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (5) 3-(S,R)-Benzyl-8-(4-chlorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (6) 3-(S)-Benzyl-8-(4-chlorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (7) 8-(2-ethylbutyryl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (8) 1,3-(S)-Dibenzyl-8-(2-ethylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (9) 8-Acetyl-1,3-(S)-dibenzyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (10) 3-(S,R)-Benzyl-8-(4-chlorobenzoyl)-1-(4-methoxybenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (11) 3-(S,R)-Benzyl-8-(4-chlorobenzoyl)-1-(4-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (12) 1,3-(S,R)-Dibenzyl-8-(4-chlorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (13) 3-(S,R)-Benzyl-8-(2-ethylbutyryl)-1-(4-methoxybenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (14) 3-(S,R)-Benzyl-8-(2-ethylbutyryl)-1-(4-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (15) 1,3-(S,R)-Dibenzyl-8-(2-ethylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (16) 1-Benzyl-8-(2-ethylbutyryl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (17) 1,3-(S)-Dibenzyl-8-(4-chlorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (18) 1,3-(S)-Dibenzyl-8-(2-ethylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (19) 8-Acetyl-1,3-(S)-dibenzyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (20) 3-(S,R)-Benzyl-8-(4-chlorobenzoyl)-1-(4-methoxybenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (21) 3-(S,R)-Benzyl-8-(4-chlorobenzoyl)-1-(4-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (22) 1,3-(S,R)-Dibenzyl-8-(4-chlorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (23) 3-(S,R)-Benzyl-8-(2-ethylbutyryl)-1-(4-methoxybenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (24) 3-(S,R)-Benzyl-8-(2-ethylbutyryl)-1-(4-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (25) 1,3-(S,R)-Dibenzyl-8-(2-ethylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (26) 1-Benzyl-8-(2-ethylbutyryl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (27) 1,3-(S)-Dibenzyl-8-(4-chlorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (28) 1-Benzyl-8-(2,4-Dimethoxybenzoyl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (29) 1,3-(S)-Dibenzyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (30) 1-Benzyl-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (31) 1,3-(S)-Dibenzyl-8-butyryl-1,4,8-triazaspiro[4.5]decan-2-one,
    (32) 1,3-(S)-Dibenzyl-8-(3-fluoro-4-trifluoromethylbenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (33) 1,3-(S)-Dibenzyl-8-(2,3-difluorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (34) 1,3-(S)-Dibenzyl-8-[2-(4-chlorophenoxy)-acetyl]-1,4,8-triazaspiro[4.5]decan-2-one,
    (35) 1,3-(S)-Dibenzyl-8-diphenylacetyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (36) 1,3-(S)-Dibenzyl-8-(2-phenoxyacetyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (37) 1,3-(S)-Dibenzyl-8-(3-phenylpropionyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (38) 1,3-(S)-Dibenzyl-8-(naphthalin-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (39) 1,3-(S)-Dibenzyl-8-(furan-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (40) 1,3-(S)-Dibenzyl-8-(3-methoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (41) 1,3-(S)-Dibenzyl-8-(4-fluorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (42) 1-Benzyl-8-(4-fluorobenzoyl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (43) 1,3-(S)-Dibenzyl-8-butyryl-1,4,8-triazaspiro[4.5]decan-2-one,
    (44) 1,3-(S)-Dibenzyl-8-(3-fluoro-4-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (45) 1,3-(S)-Dibenzyl-8-(2,3-difluorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (46) 1,3-(S)-Dibenzyl-8-[2-(4-chlorophenoxy)-acetyl]-1,4,8-triazaspiro[4.5]decan-2-one,
    (47) 1,3-(S)-Dibenzyl-8-diphenylacetyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (48) 1,3-(S)-Dibenzyl-8-(2-phenoxyacetyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (49) 1,3-(S)-Dibenzyl-8-(3-phenylpropionyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (50) 1,3-(S)-Dibenzyl-8-(naphthalin-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (51) 1,3-(S)-Dibenzyl-8-(furan-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (52) 1,3-(S)-Dibenzyl-8-(3-methoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (53) 1,3-(S)-Dibenzyl-8-(4-fluorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (54) 1-Benzyl-8-(4-fluorobenzoyl)-3-(S)-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (55) N-[4-(3-Isobutyl-2-oxo-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-8-carbonyl)-phenyl]-acetamide,
    (56) 1-(2-Phenoxyethyl)-8-(thiophene-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (57) 2-(2-Oxo-8-pent-4-enoyl-1,4,8-triazaspiro[4.5]dec-1-ylmethyl)-benzonitrile,
    (58) 8-(2,4-Dimethoxybenzoyl)-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (59) 2-[8-(2-Ethylbutyryl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (60) 4-(2-Isobutyl-3-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl)-benzonitrile,
    (61) 8-(6-Chloropyridine-3-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (62) 2-[8-(2-Methylpentanoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (63) 1-Benzyl-8-(biphenyl-4-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (64) 3-Isobutyl-8-(5-methylisoxazole-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (65) Ethyl 3-oxo-3-[2-oxo-l-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]dec-8-yl]-propionate,
    (66) 8-(2-Chlorobenzoyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (67) 8-Cyclopentanecarbonyl-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (68) 8-(Furan-2-carbonyl)-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (69) 3-Benzyl-8-(2-ethylsulfanylpyridine-3-carbonyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (70) 3-Benzyl-8-(4-chlorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (71) 8-(2-Benzyloxyacetyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (72) 3-Benzyl-8-(2-methoxyacetyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (73) 8-(5-tert.-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (74) 2-{8-[3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl]-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ytmethyl}-benzonitri!e,
    (75) 3-Benzyl-8-(2-chlorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (76) 3-Benzyl-8-(3-dimethylaminobenzoyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (77) 8-(3-Methylbenzoyl)-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (78) 3-Isopropyl-1-(3-methylbut-2-enyl)-8-(pyridine-4-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (79) 1-Benzyl-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (80) 2-{8-[3-(2-chlorophenyl)-acryloyl]-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl}-benzonitrile,
    (81) 8-(3-Chlorobenzoyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (82) Ethyl 2-(2-benzyl-3-oxo-1,4,8-triazaspiro[4.5]dec-8-yl)-2-oxo-l-phenylacetate,
    (83) 8-(3,5-Dimethoxybenzoyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (84) 3-Benzyl-8-(isoxazole-5-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (85) 8-(3-Chlorothiophene-2-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (86) 3-Isopropyl-8-pentafluorobenzoyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (87) 8-(2,5-Dimethylfuran-3-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (88) 1-Butyl-8-[2-(3,4-dimethoxyphenyl)-acetyl]-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (89) 1-Benzyl-3-isopropyl-8-(pyridin-4-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (90) 1,3-Dibenzyl-8-(3-dimethylaminobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (91) 5-{2-[1-(4-Fluorobenzyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-2-oxoethyl}-imidazolidine-2,4-dione,
    (92) 8-(Biphenyl-4-carbonyl)-1-(4-fluorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (93) 2-[2-Oxo-8-(2-propylpentanoyl)-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (94) 2-[8-(Furan-2-carbonyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (95) 8-[2-(4-Chlorophenoxy)-acetyl]-3-isobutyl-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (96) 1,3-Dibenzyl-8-(4-bromobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (97) 8-(3-Difluoromethylsulfanylbenzoyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (98) 8-(2,3-Dimethylbenzoyl)-3-isopropyl-1,4,8-triazaspiro[4,5]decan-2-one,
    (99) 3-Benzyl-8-(2,3-dimethylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (100) 1-(4-Fluorobenzyl)-3-(2-methylsulfanylethyl)-8-(pyridin-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (101) 3-Benzyl-8-(3,3-dimethylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (102) 2-[8-(3-Dimethylaminobenzoyl)-3-isobutyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (103) 3-[8-(2-Methoxyacetyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4,5]dec-1-ylmethyl]-benzonitrile,
    (104) Ethyl 2-(3-benzyl-1-methyl-2-oxo-1,4,8-triazaspiro[4,5]dec-8-yl)-2-oxo-1-phenylacetate,
    (105) 2-[8-[2-(2-Methoxyethoxy)-acetyl]-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (106) 3-Benzyl-8-[3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl]-1,4,8-triazaspiro[4.5]decan-2-one,
    (107) 8-(2-Chloro-6-fluorobenzoyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (108) 1-Methyl-3-(2-methylsulfanylethyl)-8-(2-phenoxyacetyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (109) 8-(2-Chloropyridine-3-carbonyl)-1-(4-fluorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4,5]decan-2-one,
    (110) 8-(2-Ethylbutyryl)-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4,5]decan-2-one,
    (111) 1-Methyl-3-(2-methylsulfanylethyl)-8-(2-phenoxypyridine-3-carbonyl)-1,4,8-triazaspiro[4,5]decan-2-one,
    (112) 8-(3-Fluorobenzoyl)-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (113) 3-Benzyl-8-(naphthalene-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (114) 8-Cyclohexanecarbonyl-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (115) 8-(2-Phenoxyacetyl)-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (116) 4-[1-Butyl-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]-benzonitrile,
    (117) 3-Benzyl-8-(3,3-dimethylbutyryl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (118) 3-Benzyl-8-(4-propylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (119) 3-Isopropyl-8-(2-phenoxypropionyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (120) 1-Butyl-8-hexanoyl-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (121) 8-(4-Bromo-3-methylbenzoyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (122) 8-[3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl]-3-isopropyl-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (123) 1-(2-Fluorobenzyl)-3-isobutyl-8-(3-methylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (124) 8-(2-Ethylhexanoyl)-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (125) 3-Benzyl-8-(3,4-difluorobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (126) 3-Benzyl-8-(4-ethoxybenzoyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (127) 1-Benzyl-8-(6-chloropyridine-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (128) 8-(3-Dimethylaminobenzoyl)-1-(3,5-dimethylbenzyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (129) 3-[8-(Benzo[1,3]dioxol-5-carbonyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (130) 3-Benzyl-1-methyl-8-pent-4-enoyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (131) 8-(4-Ethoxybenzoyl)-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (132) 3-Benzyl-8-(2-benzyloxyacetyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (133) 8-(3,4-Difluorobenzoyl)-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (134) 3-Benzyl-1-methyl-8-(2-methylsulfanylpyridin-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (135) 1-Butyl-8-(4-methoxybenzoyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (136) 1,3-Dibenzyl-8-(2-ethylsulfanylpyridin-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (137) 3-Benzyl-8-(3-difluoromethylsulfanylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (138) 1-(4-Fluorobenzyl)-8-(furan-2-carbonyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (139) 3-Benzyl-8-(3-fluoro-4-methylbenzoyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (140) 8-[3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl]-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (141) 1-Butyl-8-(6-Chloro-2H-chromane-3-carbonyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (142) 3-[8-(3-Methoxybenzoyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (143) 8-Cyclobutanecarbonyl-3-(2-methylsulfanylethyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (144) 3-Benzyl-1-butyl-8-(furan-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (145) 1-Benzyl-8-(3-chlorothiophene-2-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (146) 3-Benzyl-8-(2,5-bis-trifluoromethylbenzoyl)-1-butyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (147) 8-(3-Chloro-2-fluorobenzoyl)-1-(3,5-dimethylbenzyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (148) 1-Benzyl-8-(2-chloropyridin-3-carbonyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (149) 3-Isobutyi-8-pentafluorobenzoyl-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (150) 8-(2-Benzyloxyacetyl)-1-butyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4,5]decan-2-one,
    (151) 8-(Furan-2-carbonyl)-3-isobutyl-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (152) 1-Butyl-3-(2-methylsulfanylethyl)-8-(4-phenoxybutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (153) 3-Benzyl-8-(6-chloropyridine-3-carbonyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (154) 1-(2-Fluorobenzyl)-3-(2-methylsulfanylethyl)-8-(2-phenoxypyridine-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (155) 1-(2-Fluorobenzyl)-3-isobutyl-8-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (156) 8-[2-(3-Chlorophenoxy)-acetyl]-3-isopropyl-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (157) 8-(2,3-Dimethylbenzoyl)-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (158) 3-Isopropyl-8-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (159) 3-Benzyl-1-methyl-8-(5-methyl-2-phenyl-2H-[1,2,3]triazole-4-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (160) 8-[3-(2-Chlorophenyl)-5-methylisoxazole-4-carbonyl]-1-(3,5-dimethylbenzyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (161) 1-(2-Fluorobenzyl)-3-(2-methylsulfanylethyl)-8-(pyridine-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (162) 1-Benzyl-3-(2-methylsulfanylethyl)-8-(2-phenoxypyridine-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (163) 1,3-Dibenzyl-8-(3-chlorothiophene-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (164) 3-Benzyl-8-(4-tert.-butylbenzoyl)-1-methyl-1.4,8-triazaspiro[4.5]decan-2-one,
    (165) 2-[3-Isobutyl-8-(2-methoxyacetyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (166) 3-Benzyl-1-butyl-8-(5-fluoro-2-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (167) 3-Benzyl-8-[2-(4-methoxyphenyl)-acetyl]-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (168) 1,3-Dibenzyl-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (169) 1-Benzyl-3-isopropyl-8-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)-1 ,4,8-triazaspiro[4.5]decan-2-one,
    (170) 1-Benzyl-8-(4-ethoxybenzoyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (171) 3-Benzyl-1-butyl-8-cyclohexanecarbonyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (172) 3-[8-[3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl]-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (173) 1-(2-Fluorobenzyl)-3-isobutyl-8-pent-4-enoyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (174) 1-Methyl-3-(2-methylsulfanylethyl)-8-(2-propylpentanoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (175) 3-Benzyl-1-methyl-8-(2-phenoxyacetyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (176) 3-Isobutyl-1-prop-2-ynyl-8-(3-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (177) 3-Benzyl-8-(furan-2-carbonyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (178) 1-Methyl-3-(2-methylsulfanylethyl)-8-(naphthalene-1-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (179) 3-Benzyl-1-butyl-8-(3-cyclopentylpropionyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (180) 1-(3,5-Dimethylbenzyl)-3-(2-methylsulfanylethyl)-8-pentanoyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (181) 3-Benzyl-1-butyl-8-(2-methoxyacetyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (182) 3-Benzyl-8-(3-fluoro-4-trifluoromethylbenzoyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (183) 1-Benzyl-8-(3-difluoromethylsulfanylbenzoyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (184) 8-(2-Chloro-6-fluoro-3-methylbenzoyl)-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (185) Methyl 4-[3-isopropyl-8-(2-methylsulfanylpyridine-3-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (186) 8-[2-(2,5-Dimethoxyphenyl)-acetyl]-1-(2-fluorobenzyl)-3-(2-methylsulfanylethyl)-1 ,4,8-triazaspiro[4.5]decan-2-one,
    (187) 8-(5-tert.-Butyl-2-methyffuran-3-carbonyl)-3-isopropyl-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (188) 8-(2-Cyclopentoacetyl)-1-(4-fluorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (189) Methyl 4-[8-(3,3-dimethylbutyryl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (190) 3-[8-Cyclopropanecarbonyl-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (191) 3-[3-(2-Methylsulfanylethyl)-2-oxo-8-(3-trifluoromethoxybenzoyl)-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (192) 1-Butyl-8-(2-cyclopentylacetyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (193) 3-Benzyl-1-butyl-8-(pyridine-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (194) 3-Benzyl-8-[3-(2-chlorophenyl)-acryloyl]-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (195) Methyl 4-[8-(3-fluoro-4-trifluoromethylbenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (196) 8-[3-(2,6-Dichlorophenyl)-5-methylisoxazole-4-carbonyl]-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (197) 1-Butyl-8-cyclohexanecarbonyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (198) 3-Benzyl-1-butyl-8-(4-iodobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one
    (199) 1-Methyl-3-(2-methylsulfanylethyl)-8-[3-(3-trifluoromethylphenyl)-acryloyl]-1,4,8-triazaspiro[4.5]decan-2-one,
    (200) 1,3-Dibenzyl-8-(4-phenoxybutyryl)-1,4,8-triazaspiro[4.5]decan-2-one
    (201) 3-Benzyl-8-(2-chloro-6-fluorobenzoyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (202) Methyl 4-[8-(2-chloropyridine-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (203) 8-(2,5-Dimethylfuran-3-carbonyl)-3-isopropyl-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (204) 8-(Biphenyl-4-carbonyl)-3-(2-methylsulfanylethyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (205) 8-(3-Chlorothiophene-2-carbonyl)-3-(2-methylsulfanylethyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (206) 1-(4-Fluorobenzyl)-8-[2-(4-methoxyphenyl)-acetyl]-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (207) 1-Benzyl-3-isopropyl-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (208) 2-[3-Isopropyl-8-(2-methylsulfanylpyridin-3-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (209) 3-[8-(5-tert.-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-3-isobutyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (210) 1-Butyl-8-(2,5-dimethylfuran-3-carbonyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (211) 8-(3-Cyclopentylpropionyl)-1-(2-fluorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (212) 1-Benzyl-8-(3-cyclopentylpropionyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (213) 3-(2-Methylsulfanylethyl)-8-(4-phenoxybutyryl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (214) 1,3-Dibenzyl-8-(3-phenylacryloyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (215) 3-Benzyl-8-(6-chloro-2-fluoro-3-methylbenzoyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (216) 8-[3-(2-Chlorophenyl)-acryloyl]-3-isopropyl-1-(2-phenoxyethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (217) 2-[3-Isopropyl-2-oxo-8-(3-phenylacryloyl)-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (218) 3-Benzyl-1-methyl-8-(4-methyl-3-nitrobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (219) 1-Benzyl-8-(furan-2-carbonyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (220) 1-Butyl-8-(3,5-dimethoxybenzoyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (221) 1,3-Dibenzyl-8-(3,3-dimethylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (222) 8-(2,6-Difluoro-3-methylbenzoyl)-1-methyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (223) 2-[8-(2-Chloro-6-fluorobenzoyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (224) 8-[3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl]-3-isopropyl-1-(3-methylbut-2-enyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (225) 3-Isobutyl-1-prop-2-ynyl-8-(4-trifluoromethoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (226) 1-Benzyl-8-(2-chloro-6-fluoro-3-methylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (227) Benzyl 2-(1-benzyl-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl)benzoate,
    (228) 1,3-Dibenzyl-8-(2-phenylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (229) 3-Benzyl-1-methyl-8-(4-nitrobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (230) 3-Benzyl-1-methyl-8-(5-methylisoxazole-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (231) 1-Benzyl-8-(6-chloro-2-fluoro-3-methylbenzoyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (232) 1-Benzyl-8-(3-fluoro-4-trifluoromethylbenzoyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (233) 3-Benzyl-8-(6-chloro-2H-chromane-3-carbonyl)-1-methyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (234) 3-Benzyl-1-butyl-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (235) 3-Benzyl-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (236) 2-[8-(6-Chloro-2H-chromane-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (237) 2-[8-(5-Methylisoxazole-3-carbonyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (238) 2-[8-(3-Chloro-2-fluorobenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (239) Methyl 4-[8-(5-tert.-butyl-2-methyl-2H-pyrazole-3-carbonyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (240) 3-Benzyl-1-butyl-8-(5-tert.-butyl-2-methyl-2H-pyrazole-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (241) 3-Benzyl-1-butyl-8-(2-chloro-4-trifluoromethylpyrimidine-5-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (242) 3-Benzyl-8-(5-methylisoxazole-3-carbonyl)-1-prop-2-ynyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (243) Methyl 4-[8-(2-chloropyridine-3-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (244) 8-(2-tert.-Butyl-5-methyl-2H-pyrazole-3-carbonyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (245) Methyl 4-[8-(2-methylsulfanylpyridine-3-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (246) Butyl 4-[8-(4-acetylaminobenzoyl)-3-isobutyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (247) Ethyl [8-(4-acetylaminobenzoyl)-3-benzyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (248) Butyl 4-[8-(2-ethylsulfanylpyridine-3-carbonyl)-3-isobutyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (249) Methyl 4-[8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (250) 4-[1-Allyl-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]-benzolsulfonamide,
    (251) Methyl 4-(8-cyclobutanecarbonyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl)benzoate,
    (252) Ethyl 2-[1-allyl-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-2-oxo-acetate,
    (253) 8-(Biphenyl-4-carbonyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (254) Ethyl [3-(2-Methylsulfanylethyl)-2-oxo-8-propionyl-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (255) 8-(Benzo[1,3]dioxole-5-carbonyl)-1-(2,6-dichlorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (256) 1-Allyl-8-(biphenyl-4-carbonyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (257) Ethyl [3-benzyl-8-(biphenyl-4-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (258) Ethyl [8-(3-dimethylaminobenzoyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (259) 3-(2-Oxo-8-pentanoyl-1,4,8-triazaspiro[4.5]dec-1-ylmethyl)-benzonitrile,
    (260) Methyl 4-(8-cyclopentanecarbonyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl)benzoate,
    (261) Ethyl 4-[1-(2-fluorobenzyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-4-oxo-butanoate,
    (262) 1-(2-Fluorobenzyl)-8-(3,4,5-trimethoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (263) Methyl 4-[8-(2-chloropyridine-4-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (264) 3-[8-(3,5-Bis-trifluoromethylbenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (265) 3-Benzyl-1-(2-fluorobenzyl)-8-(2-methoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (266) 8-(Benzo[1,2,5]oxadiazole-5-carbonyl)-1-(2,6-dichlorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (267) Ethyl [3-benzyl-2-oxo-8-(4-sulfamoylbenzoyl)-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (268) 3-[2-Oxo-8-(3,4,5-trimethoxybenzoyl)-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (269) Ethyl 2-[1-(4-acetoxybutyl)-3-isobutyl-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-1,1-dimethyl-2-oxo-acetate,
    (270) 8-(6-Chloropyridine-3-carbonyl)-1-(2,6-dichlorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (271) 8-(2-Ethoxybenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (272) 1-Allyl-8-cyclopropanecarbonyl-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (273) 3-[3-lsopropyl-8-(2-methoxyacetyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (274) Methyl 4-(2-oxo-8-phenylacetyl-1,4,8-triazaspiro[4.5]dec-1-ylmethyl)benzoate,
    (275) Ethyl 2-[1-(3-cyanobenzyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-2-oxo-1-phenylacetate,
    (276) 1-(2-Fluorobenzyl)-8-(4-methoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (277) Methyl 4-(8-cyclohexanecarbonyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl)benzoate,
    (278) 1-(2-Fluorobenzyl)-8-pent-4-enoyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (279) Ethyl [3-isobutyl-8-(3-ethylbutyryl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (280) 1-Allyl-8-(3,3-dimethylbutyryl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (281) 1-Allyl-3-(2-methylsulfanylethyl)-8-(2-methylsulfanylpyridin-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (282) Ethyl [3-isobutyl-8-(2-Methylpentanoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (283) Methyl 4-[8-(5-tert.-butyl-2-methylfuran-3-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (284) Ethyl (3-benzyl-8-cyclopropanecarbonyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl)acetate,
    (285) Ethyl [3-benzyl-8-(3-methylbutyryl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (286) 1-(2,6-Dichlorobenzyl)-8-(2,5-dimethylfuran-3-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (287) 1-Allyl-3-isopropyl-8-[2-(3-methoxyphenyl)-acetyl]-1,4,8-triazaspiro[4.5]decan-2-one,
    (288) Ethyl [8-(4-tert.-butylbenzoyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (289) 3-(2-Methylsulfanylethyl)-1-(2-nitrobenzyl)-8-(2-phenoxypyridine-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (290) Ethyl (3-benzyl-2-oxo-8-pentanoyl-1,4,8-triazaspiro[4.5]dec-1-yl)acetate,
    (291) 8-(2-Chloropyridine-4-carbonyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one.
    (292) Ethyl [8-(3-methylbutyryl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (293) 1-Allyl-3-(2-methylsulfanylethyl)-8-pentafluorobenzoyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (294) 1-(2-Fluorobenzyl)-8-(2-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (295) 8-(Benzo[1,2,5]oxadiazole-5-carbonyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (296) Methyl 4-[8-(4-tert.-butylbenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]benzoate,
    (297) Ethyl [3-benzyl-2-oxo-8-(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (298) 1-Allyl-3-isopropyl-8-pent-4-enoyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (299) 3-[2-Oxo-8-(2-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (300) 8-(2-Dimethylaminoacetyl)-1-(3,5-dimethylbenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (301) Butyl [8-(2-ethoxybenzoyl)-3-isobutyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (302) 1-(2-Fluorobenzyl)-8-(3-methoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (303) Ethyl [8-(furan-2-carbonyl)-3-isobutyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (304) 8-(5-tert.-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (305) 1-(2-Fluorobenzyl)-8-(thiophene-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (306) Ethyl [3-benzyl-8-(2-fluorobenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (307) Ethyl [8-(isoxazole-5-carbonyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (308) 1-(2,6-Dichlorobenzyl)-3-isobutyl-8-(4-propylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (309) Ethyl [8-[2-(2,5-dimethoxyphenyl)-acetyl]-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (310) Ethyl (3-benzyl-8-cyclobutanecarbonyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl)acetate,
    (311) 1-(2-Fluorobenzyl)-8-[2-(4-methoxyphenyl)-acetyl]-1,4,8-triazaspiro[4.5]decan-2-one,
    (312) 1-Allyl-3-(2-methylsulfanylethyl)-8-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (313) Ethyl [3-(2-methylsulfanylethyl)-2-oxo-8-(4-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (314) 1-Allyl-3-(2-methylsulfanylethyl)-8-(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (315) 1-(2,6-Dichlorobenzyl)-8-(2,3-difluoro-4-methylbenzoyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (316) 1-Allyl-3-isopropyl-8-(2-methylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (317) 8-(2-Chloro-5-trifluoromethylbenzoyl)-1-(2,6-dichlorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (318) 1-Allyl-8-[2-(3-methoxyphenyl)-acetyl]-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (319) 1-Allyl-3-(2-methylsulfanylethyl)-8-(3-phenylpropionyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (320) Ethyl [3-benzyl-8-(2-benzyloxyacetyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (321) 1-Allyl-8-(5-tert.-butyl-2-methyl-2H-pyrazole-3-carbonyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (322) Ethyl 1,1-dimethyl-2-[3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-2-oxo-acetate,
    (323) Benzyl 2-[1-ethoxycarbonylmethyl-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]benzoate,
    (324) 1-Allyl-3-isopropyl-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (325) 1-Allyl-8-(2,5-dimethylfuran-3-carbonyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (326) 1-Allyl-8-(benzo[1,2,5]oxadiazole-5-carbonyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (327) 1-(2-Fluorobenzyl)-8-(4-phenoxybutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (328) 1-Allyl-8-(2-cydopentylacetyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (329) Ethyl [3-benzyl-8-(naphthalene-2-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (330) 8-[3-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl]-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (331) 3-[8-(3,5-Dimethoxybenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (332) 3-(2-Methylsulfanylethyl)-1-(2-nitrobenzyl)-8-(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (333) Ethyl {3-benzyl-8-[3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl]-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl}acetate,
    (334) 1-(2-Fluorobenzyl)-8-(3-fluoro-4-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (335) Ethyl [8-[1-(4-chlorophenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl]-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (336) 3-[8-(Naphthalene-1-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (337) Ethyl [8-(3,3-dimethylbutyryl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (338) 8-Acetyl-3-(2-methylsulfanylethyl)-1-naphthalen-2-ylmethyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (339) Ethyl [3-benzyl-8-(3-cyanobenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (340) 8-(5-tert.-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-1-(2,6-dichlorobenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (341) 4-[3-Benzyl-1-(2-fluorobenzyl)-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]-benzonitrile,
    (342) Methyl 4-[3-benzyl-1-(2-fluorobenzyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-4-oxo-butyrate,
    (343) 3-(2-Methylsulfanylethyl)-1-naphthalen-2-ylmethyl-8-(3,4,5-trimethoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (344) Ethyl [3-benzyl-8-(isoxazole-5-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (345) 8-(3-Difluoromethylsulfanylbenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (346) Ethyl [3-benzyl-8-(2,3-dimethylbenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (347) 1-(2-Fluorobenzyl)-8-(4-propylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (348) 3-[8-(4-Iodobenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (349) 1-(2-Fluorobenzyl)-8-(2-propylpentanoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (350) 3-[8-(2,6-Difluoro-3-methylbenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (351) 3-(2-Methylsulfanylethyl)-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (352) Butyl 4-[3-isobutyl-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (353) 8-[2-(4-Chlorophenoxy)-acetyl]-3-(2-methylsulfanylethyl)-1-naphthalen-2-ylmethyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (354) Ethyl [3-benzyl-2-oxo-8-(3-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (355) 8-(4-Bromobenzoyl)-3-(2-methylsulfanylethyl)-1-naphthalen-2-ylmethyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (356) Ethyl [8-(2-chloropyridine-4-carbonyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (357) 1-Allyl-8-(3,5-dimethoxybenzoyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (358) 3-[8-(4-Methyl-3-nitrobenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (359) 8-(4-tert.-Butylbenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (360) 1-Allyl-3-isopropyl-8-(5-methylisoxazole-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (361) 1-Allyl-3-(2-methylsulfanylethyl)-8-(2-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (362) Ethyl [3-benzyl-8-(3-cyclopentylpropionyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (363) 3-Benzyl-8-(3,5-difluorobenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (364) Ethyl [3-benzyl-8-(5-fluoro-2-trifluoromethylbenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (365) Ethyl [3-benzyl-2-oxo-8-(3,4,5-trimethoxybenzoyl)-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (366) Benzyl 2-[1-(2-fluorobenzyl)-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]benzoate,
    (367) 1-(2-Fluorobenzyl)-8-(2-methylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (368) 1-(2-Fluorobenzyl)-8-(2-phenylbutyryl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (369) 1-Allyl-8-(6-chloropyridine-3-carbonyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (370) Ethyl [8-(2,5-dimethylfuran-3-carbonyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (371) Ethyl [8-(5-tert.-butyl-2-methyl-2H-pyrazole-3-carbonyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (372) Benzyl 2-[1-allyl-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]benzoate,
    (373) Ethyl 2-[1-allyl-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-8-yl]-2-oxo-1-phenylacetate,
    (374) 3-[8-(2-Chloro-6-fluorobenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (375) 3-(2-Methylsulfanylethyl)-1-(2-nitrobenzyl)-8-(3-phenylpropionyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (376) 3-[8-(2,3-Dimethylbenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (377) Ethyl [8-(5-fluoro-2-trifluoromethylbenzoyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (378) Ethyl [8-cyclopentanecarbonyl-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (379) Ethyl [3-(2-methylsulfanylethyl)-2-oxo-8-(thiophene-2-carbonyl)-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (380) 1-Allyl-8-[1-(4-chlorophenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl]-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (381) 1-Allyl-3-(2-methylsulfanylethyl)-8-(naphthalene-1-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (382) 1-(2-fluorobenzyl)-8-(4-trifluoromethoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (383) 3-Benzyl-8-(2-benzyloxyacetyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (384) 3-[8-(2-chloro-6-fluoro-3-methylbenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (385) 1-Allyl-8-(2-chloro-5-trifluoromethylbenzoyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (386) 8-(3-Methylbenzoyl)-3-(2-methylsulfanylethyl)-1-naphthalen-2-ylmethyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (387) 1-(3,5-Dimethylbenzyl)-8-(2-ethylbutyryl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (388) 8-(5-tert.-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (389) Benzyl 2-[1-(3-cyanobenzyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]benzoate,
    (390) 8-(4-Methyl-3-nitrobenzoyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (391) 1-(2,6-Dichlorobenzyl)-3-isobutyl-8-(3,4,5-trimethoxybenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (392) 3-{8-[2-(2-Bromophenyl)-acetyl]-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl}-benzonitrile,
    (393) 3-[8-(2,3-Dichlorobenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (394) 1-Allyl-8-(6-chloro-2H-chromane-3-carbonyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (395) Ethyl {3-benzyl-8-[2-(4-methoxyphenyl)-acetyl]-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl}acetate,
    (396) 3-[3-Isopropyl-2-oxo-8-(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (397) 8-(3-Cyclopentylpropionyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (398) 1-Allyl-8-(3-difluoromethylsulfanylbenzoyl)-3-isopropyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (399) 3-[8-(2-chloro-4-nitrobenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (400) Ethyl [8-(2-ethoxybenzoyl)-3-(2-methylsulfanylethyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (401) 8-(2,5-Bis-trifluoromethylbenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (402) 8-(2-Chloropyridine-4-carbonyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (403) Ethyl {3-benzyl-8-[3-(2,6-dichlorophenyl)-5-methylisoxazole-4-carbonyl]-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl}acetate,
    (404) 1-(3,5-Dimethylbenzyl)-3-isobutyl-8-(2-trifluoromethylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (405) 8-(3,5-Dimethoxybenzoyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (406) Benzyl 2-[3-benzyl-1-(2-fluorobenzyl)-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]benzoate,
    (407) 3-[8-(Benzo[1,2,5]oxadiazole-5-carbonyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (408) Ethyl [3-(2-methylsulfanylethyl)-2-oxo-8-(4-trifluoromethoxybenzoyl)-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (409) 1-Allyl-3-isopropyl-8-[2-(4-methoxyphenyl)-acetyl]-1,4,8-triazaspiro[4.5]decan-2-one,
    (410) 3-(2-Methylsulfanylethyl)-1-(2-nitrobenzyl)-8-(4-propylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (411) 3-Benzyl-8-(4-tert.-butylbenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (412) 1-Allyl-8-(2,6-difluoro-3-methylbenzoyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (413) 8-(3,5-Bis-trifluoromethylbenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (414) 3-[8-(4-Iodobenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (415) 3-(2-Methylsulfanylethyl)-1-naphthalen-2-ylmethyl-8-(thiophene-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (416) Ethyl [3-benzyl-8-(2-chloropyridine-4-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (417) Ethyl [3-(2-methylsulfanylethyl)-8-(4-nitrobenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (418) 8-(2-Ethylhexanoyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (419) 1-(2,6-Dichlorobenzyl)-3-isobutyl-8-(thiophene-2-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (420) Ethyl [3-benzyl-8-(2-chloro-4-nitrobenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (421) 3-Benzyl-8-(3,5-bis-trifluoromethylbenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (422) Ethyl [3-benzyl-8-(4-bromo-3-methylbenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (423) 8-Cyclohexanecarbonyl-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (424) 8-(2,5-Dimethylfuran-3-carbonyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (425) 8-(3-Difluoromethylsulfanylbenzoyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (426) 8-(Furan-2-carbonyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (427) Ethyl [3-benzyl-8-(2,3-difluorobenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (428) 3-[3-Isopropyl-8-(4-methyl[1,2,3]thiadiazole-5-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (429) 3-[8-(3-Chloro-2-fluorobenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (430) Ethyl [3-benzyl-8-(naphthalene-1-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (431) 8-(4-tert.-Butylbenzoyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (432) 3-[3-Benzyl-1-(2-fluorobenzyl)-2-oxo-1,4,8-triazaspiro[4.5]decan-8-carbonyl]-benzonitrile,
    (433) 1-(2,6-Dichlorobenzyl)-8-(furan-2-carbonyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (434) 8-(2,6-Dichlorobenzoyl)-1-(2-fluorobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (435) 1-(3,5-Dimethylbenzyl)-8-(3-fluoro-4-trifluoromethylbenzoyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (436) 1-(2-Fluorobenzyl)-8-(3-fluoro-4-methylbenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (437) 1-Allyl-8-(3-cyclopentylpropionyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (438) 8-[2-(3-Chlorophenoxy)-acetyl]-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (439) 1-(3,5-Dimethylbenzyl)-3-isobutyl-8-(2-methylsulfanylpyridine-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (440) 3-(2-Methylsulfanylethyl)-1-(2-nitrobenzyl)-8-propionyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (441) 3-[8-(3,4-Dimethoxybenzoyl)-3-isopropyl-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (442) 3-(2-Methylsulfanylethyl)-8-(naphthalene-2-carbonyl)-1-naphthalen-2-ylmethyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (443) 8-(6-Chloro-2H-chromane-3-carbonyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (444) Ethyl {3-benzyl-2-oxo-8-[3-(3-trifluoromethylphenyl)-acryloyl]-1,4,8-triazaspiro[4.5]dec-1-yl}acetate,
    (445) 1-(3,5-Dimethylbenzyl)-3-isobutyl-8-(3-phenylacryloyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (446) 3-[3-Isopropyl-2-oxo-8-(2-phenoxypropionyl)-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (447) 3-[3-Isopropyl-2-oxo-8-(4-trifluoromethoxybenzoyl)-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile,
    (448) 1-Allyl-3-(2-methylsulfanylethyl)-8-(3-nitrobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (449) Ethyl [3-benzyl-8-(3,4-dichlorobenzoyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-yl]acetate,
    (450) 1-(2-Fluorobenzyl)-8-[3-(3-trifluoromethylphenyl)-acryloyl]-1,4,8-triazaspiro[4.5]decan-2-one,
    (451) 1-Allyl-8-(3,5-bis-trifluoromethylbenzoyl)-3-(2-methylsulfanylethyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (452) 8-(3-Cyclopentylpropionyl)-3-(2-methylsulfanylethyl)-1-(2-nitrobenzyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (453) 1-(3,5-Dimethylbenzyl)-3-isobutyl-8-(4-nitrobenzoyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    (454) 8-(3-Cyclopentylpropionyl)-1-(3,5-dimethylbenzyl)-3-isobutyl-1,4,8-triazaspiro[4.5]decan-2-one,
    (455) 3-[3-Isopropyl-8-(isoxazole-5-carbonyl)-2-oxo-1,4,8-triazaspiro[4.5]dec-1-ylmethyl]-benzonitrile und
    (456) 3-Benzyl-1-(2-fluorobenzyl)-8-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)-1,4,8-triazaspiro[4.5]decan-2-one,
    in each case optionally in the form of one of the pure stereoisomers thereof, particularly enantiomers or diastereoisomers thereof, the racemates thereof or in the form of a mixture of stereoisomers thereof, particularly the enantiomers and/or diastereoisomers, in any desired mixing ratio, or in each case in the form of corresponding salts, or in each case in the form of corresponding solvates.
  14. A process for the production of the substituted 1,4,8-triazaspiro[4.5]decan-2-one compounds according to one or more of claims 1 to 13, characterized in that a protected piperidin-4-one of the general formula II,
    Figure imgb0028
     in which P stands for a protective group, is converted, by reaction with at least one compound of the general formula III,
    Figure imgb0029
     in which R2 has the meaning according to one or more of claims 1 to 13, into at least one compound of the general formula IV,
    Figure imgb0030
     in which P and R2 have the aforementioned meanings, which is optionally purified and/or optionally isolated, and optionally converted, by reaction with at least one compound of the general formula R1-X1, in which R1 has the meaning according to one or more of claims 1 to 13 and X1 stands for a suitable leaving group, preferably for a halogen residue, optionally in the presence of at least one base, into at least one compound of the general formula V,
    Figure imgb0031
     in which R1, R2 and P have the aforementioned meanings, which compound is optionally purified and/or optionally isolated, and optionally converted, by splitting-off the protective group P, into at least one compound of the general formula VI,
    Figure imgb0032
     which compound is optionally purified and/or optionally isolated, and optionally at least one compound of the general formula IV, V or VI is converted, by reaction with a carboxylic acid derivative of the general formula R4-(C=O)-X2, a carboxylic anhydride of the general formula (R4-(C=O))2O or a compound of the general formula R3-X3, in which the residue R3 has the meaning according to one of claims 1 to 13 with the exception of hydrogen and -(C=O)-R4, R4 in each case has the meaning according to one or more of claims 1 to 13 and X2 and X3 in each case stand for a suitable leaving group, preferably for a halogen residue, into at least one compound according to one or more of claims 1 to 13, and the latter compound is optionally purified and/or optionally isolated,
    or
    4-piperidone of the formula VII, optionally in the form of a corresponding salt,
    Figure imgb0033
     is converted, by reaction with a carboxylic acid derivative of the general formula R4-(C=O)-X2, a carboxylic anhydride of the general formula (R4-(C=O))2O or a compound of the general formula R3-X3,
    in which R3 has the meaning according to one or more of claims 1 to 13 with the exception of hydrogen and (C=O)-R4, the residue R4 in each case has the aforementioned meaning and X2 and X3 each stand for a suitable leaving group, preferably for a halogen residue, into a compound of the general formula VIII,
    Figure imgb0034
     in which R3 has the meaning according to one or more of claims 1 to 13, this being optionally purified and/or isolated and converted, by reaction with at least one compound of the general formula III
    Figure imgb0035
     in which R2 has the aforementioned meaning, into at least one compound of the general formula IX,
    Figure imgb0036
     in which R2 and R3 each have the aforementioned meanings, this being optionally purified and/or isolated and optionally converted, by reaction with at least one compound of the general formula R1-X1
    in which R1 and X1 have the aforementioned meanings, optionally in the presence of at least one base, into at least one compound according to one or more of claims 1 to 13, which is optionally purified and/or isolated.
  15. A medicament containing at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to one or more of claims 1 to 13 and optionally one or more pharmaceutically acceptable adjuvants.
  16. A medicament according to claim 15 for regulation, particularly inhibition, of noradrenalin reuptake (noradrenalin-uptake), for regulation, particularly inhibition, of 5-hydroxy tryptophan reuptake (5-HT uptake), for opioid receptor regulation, particularly for µ-opioid receptor regulation, and/or for batrachotoxin (BTX) receptor regulation.
  17. A medicament according to claim 15 or claim 16 for prophylaxis and/or treatment of disturbances in food intake, preferably selected from the group consisting of bulimia, anorexia, obesity, and cachexia, preferably obesity.
  18. A medicament according to claim 15 or claim 16 for prophylaxis and/or treatment of pain, preferably for treatment and prophylaxis of acute pain, chronic pain, neuropathic pain, and/or cluster headache.
  19. A medicament according to claim 15 or claim 16 for prophylaxis and/or treatment of depression.
  20. A medicament according to claim 15 or claim 16 for combined prophylaxis and/or treatment of depression and pain, preferably for combined treatment of depression and pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and cluster headache.
  21. A medicament according to claim 15 or claim 16 for prophylaxis and/or treatment of abuse of alcohol and/or drugs and/or medicines, for prophylaxis and/or treatment of addiction to alcohol and/or drugs and/or medicines, for prophylaxis and/or treatment of inflammations, for prophylaxis and/or treatment of lethargy, for prophylaxis and/or treatment of ischemia, for prophylaxis and/or treatment of catalepsy, for vigilance enhancement, for libido enhancement, for anxiolysis, for prophylaxis and/or treatment of neurodegenerative disorders, preferably one or more neurodegenerative disorders selected from the group consisting of Parkinson's disease, Huntington's chorea, Alzheimer's disease and multiple sclerosis, and/or for local anaesthesia.
  22. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 including the excluded compounds for the production of a medicament for regulation of noradrenalin reuptake (noradrenalin uptake), preferably for inhibition of noradrenalin reuptake (noradrenalin uptake).
  23. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 including the excluded compounds for the production of a medicament for regulation of 5-hydroxy tryptophan reuptake (5-HT uptake), preferably for inhibition of 5-hydroxy tryptophan reuptake (5-HT uptake).
  24. The use at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 including the excluded compounds for the production of a medicament for opioid receptor regulation, preferably for µ-opioid receptor regulation.
  25. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 including the excluded compounds for the production of a medicament for batrachotoxin (BTX) receptor regulation.
  26. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound of the general formula I according to any one of claims 1 to 13 including the excluded compounds for the production of a medicament for prophylaxis and/or treatment of disturbances in food intake, preferably selected from the group consisting of bulimia, anorexia, obesity, and cachexia, particularly preferably obesity.
  27. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound of the general formula I according to any one of claims 1 to 13 including the excluded compounds listed under B) but excluding the compounds listed under A) for the production of a medicament for prophylaxis and/or treatment of pain.
  28. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 including the excluded compounds for the production of a medicament for prophylaxis and/or treatment of acute pain, chronic pain, neuropathic pain and/or cluster headache.
  29. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 including the excluded compounds listed under B) but excluding the compounds listed under A) for the production of a medicament for prophylaxis and/or treatment of depression.
  30. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 including the excluded compounds for prophylaxis and/or treatment of the abuse of drugs and medicines, for prophylaxis and/or treatment of addiction to drugs and/or medicines, for prophylaxis and/or treatment of multiple sclerosis, for prophylaxis and/or treatment of lethargy, for prophylaxis and/or treatment of catalepsy, for vigilance enhancement, for libido enhancement, for anxiolysis, for prophylaxis and/or treatment of ischemia and/or for local anaesthesia.
  31. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 including the excluded compounds listed under B) but excluding the compounds listed under A) for the production of a medicament for prophylaxis and/or treatment of alcohol abuse, for prophylaxis and/or treatment of alcohol addiction and/or for prophylaxis and/or treatment of inflammations.
  32. The use of at least one substituted 1,4,8-triazaspiro[4.5]decan-2-one compound according to any one of claims 1 to 13 for the production of a medicament for prophylaxis and/or treatment of neurodegenerative disorders, preferably one or more disorders selected from the group consisting of Huntington's chorea, Alzheimer's disease and Parkinson's disease.
EP05716285A 2004-03-22 2005-03-22 Substituted 1,4,8-triazaspiro[4,5]decan-2-on compounds for use in the treatment of obesity Active EP1730147B1 (en)

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PL05716285T PL1730147T3 (en) 2004-03-22 2005-03-22 Substituted 1,4,8-triazaspiro[4,5]decan-2-on compounds for use in the treatment of obesity
SI200530982T SI1730147T1 (en) 2004-03-22 2005-03-22 SUBSTITUTED 1,4,8-TRIAZASPIRO?á4,5?åDECAN-2-ON COMPOUNDS FOR USE IN THE TREATMENT OF OBESITY
CY20101100325T CY1109962T1 (en) 2004-03-22 2010-04-09 Substituted 1,4,8-Triazaspiro [4,5] DECAN-2-ONE COMPOUNDS FOR OBESITY TREATMENT

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